Glossary

3-Abz (m-aminobenzoic acid) can be considered a γ-amino acid. Incorporation of m-aminobenzoic acid into peptide chains generates a rigid turn.

4-Abz (p-Aminobenzoic acid, PABA) a naturally occurring benzoic acid derivative, can also be used as an rigid linear spacer.

Abu (L-α-Aminobutyric acid) is a non-polar amino acid, a homolog of Ala and an isostere of Ser and Cys.

Abz (2-aminobenzoic acid or anthranilic acid), a fluorophore (excitation at 320 nm, emission at 420 nm).

Ac stands for acetyl. N-terminal acetylation is a common stabilizing modification of peptides in nature.

Acetamidomethyl. The sulfhydryl protecting group Acm is compatible with Fmoc and Boc chemistry. Acm is cleaved by Hg(II) or Ag(I) or by iodine with concomitant oxidation. When synthesizing peptides containing two disulfide bridges via consecutive S-S- bond formation, Acm is often chosen in combination with acid-labile thiol protection.

Adrenocorticotropic hormone (ACTH) is an anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids.

Aad (L-α-aminoadipic acid) is a homolog of Glu, i.e. contains an additional methylene group.

1-(1′-Adamantyl)-1-methyl-ethoxycarbonyl, an adamantane-derived very acid-labile amino-protecting group cleaved by 3% TFA/methylene chloride.

8-Amino-3,6-dioxa-octanoic acid, polar, flexible spacer of 9 atoms.

7-Amido-4-trifluoromethylcoumarin, a fluorophore usually incorporated C-terminally in carboxypeptidase substrates. Excitation of the released coumarin at 395-400 nm, emission at 495-505 nm.

α-Aminoglycine, the simplest α,α-diamino acid, which is only available in N-protected form.

Aib, α-Aminoisobutyric acid, is the simplest α-alkylated amino acid. The designation “peptaibols” for this class of fungal peptide antibiotics is due to their large Aib content.

Allyloxycarbonyl, an amino-protecting group (also abbreviated as Alloc) compatible with Fmoc- and Boc chemistry. It is selectiviely cleaved by Pd(PPh3)4. See also OAll.

7-Amido-4-methylcoumarin (AMC, MCA, or NHMec), a fluorophore incorporated C-terminally in carboxypeptidase substrates. Excitation of the released coumarin at 360-380 nm, emission at 440-460 nm.

Molecules containing an amine group, a carboxylic acid group and a side chain that varies between different amino acids.

Amino acids are molecules containing an amine group, a carboxylic acid group and a side chain that varies between different amino acids. These molecules contain the key elements of Carbon, Hydrogen, Oxygen, and Nitrogen. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent.[1] In an alpha amino acid, the amino and carboxylate groups are attached to the same carbon atom, which is called the α–carbon. The various alpha amino acids differ in which side chain (R group) is attached to their alpha carbon. These side chains can vary in size from just a hydrogen atom in glycine, to a methyl group in alanine, through to a large heterocyclic group in tryptophan.

Atrial natriuretic factor (ANF or ANP) is a potent natriuretic and vasodilatory peptide. ANF is secreted mainly by the heart atrium and plays an important role in blood volume and blood pressure homeostasis.

2-Aminooxyacetic acid (AOAc) is used for introducing a hydroxylamine moiety, which reacts with aldehydes and ketones yielding oximes. This highly selective reaction has found use in peptide ligation. AOAc can also be inserted in peptides.

α-Aminosuberic acid, an α-amino-α,ω-dicarboxylic acid and hence a homolog of Asp, Glu, and Aad. Asu has been used as a carba disulfide bond mimic, e.g. in elcatonin.

ε-Aminohexanoic acid (ε-Aminocaproic acid, also abbreviated Aca or LC) is often introduced as short non-polar spacer, e.g. between the N-terminus of a peptide and biotin, between Nε of Lys and a fluorophore.

Bovine adrenal medulla. The adrenal medulla is the inner portion of the adrenal gland. It consists mainly of chromaffin cells that produce and store a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine.

Brain natriuretic peptide (BNP) is a natriuretic, diuretic and vasodilatory factor that is secreted by the brain and the heart atria.

t-Butyloxycarbonyl (Boc) is an acid-labile temporary Nα-protecting group employed in solution synthesis and in SPPS (Boc/Bzl-based SPPS). Common cleavage reagents are TFA/methylene chloride (1:1), HCl in ethyl acetate or dioxane, 98% formic acid.

t-Butyloxycarbonyl (Boc) is an acid-labile temporary Nα-protecting group employed in solution synthesis and in SPPS (Boc/Bzl-based SPPS). Common cleavage reagents are TFA/methylene chloride (1:1), HCl in ethyl acetate or dioxane, 98% formic acid.

Benzyloxymethyl (Bom), an acid-labile imidazole protecting group used during Boc-SPPS of His-containing peptides. As an acetal, Bom yields highly reactive formaldehyde upon acid treatment. Thus, Bom is best removed in the presence of Cys, methoxyamine or other compounds reacting with the aldehyde.

2-(4-Biphenylyl)isopropyloxycarbonyl (Bpoc) is a highly acid-labile temporary Nα-protecting group. It is cleaved e.g. with 1% TFA/methylene chloride.

Bovine serum albumin, serum albumin from cows, commonly used in in vitro biological studies.

t-Butyldimethylsilyl (Bsi or BDMS), a hydroxyl protecting group compatible with Fmoc-SPPS. Bsi is acid-labile, but it can be cleaved selectively by action of fluoride ions.

Benzoyl, an acyl group often N-terminally introduced, less polar than acetyl (Ac). A permanent modification of a peptide.

Benzyl (Bzl) an alkyl residue and a side-chain protecting group employed in Boc/Bzl-based SPPS and solution synthesis. Bzl is commonly used for blocking alcohols (Ser, Thr, Hyp), it is cleaved by strong acids or catalytic hydrogenolysis (e.g. hydrogen/Pd). Deblocking of N-Bzl and S-Bzl requires much harsher conditions. The acid lability of benzyl ethers, esters (see OBzl), thiols, and amines can be modulated by introducing  substituents at the α-carbon or the aromat, e.g. halogens for improving or α-substituents for decreasing the acid stability.

Cholecystokinin (CCK) is a peptide hormone secreted by the upper intestinal mucosa. It is also found in the central nervous system. CCK causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions.

Certificate of Suitability.

Colony-forming unit for monocytes.

Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide which belongs to a family of related peptidesincluding calcitonin, amylin, and adrenomedullin. It exists in two isoforms α-CGRP (or CGRP I) and β-CGRP(or CGRP II) which are very similar in their biological activities and are encoded by different genes. CGRP peptides are mainly localized in sensory and central neurons and have been implicated in a variety of physiological processes such as cardiovascular homeostasis, calcium metabolism, and control of fetoplacental vascular tone. Receptors for this family of peptides belong to the seven transmembrane G-protein-coupled receptors linked to theactivation of adenylate cyclase. Their interaction with receptor activity modifying proteins (RAMPs) is essential formembrane trafficking and for conferring ligand specificity.

L-Cyclohexylalanine, a non-polar amino acid. As cyclohexylalanine corresponds to per-hydrogenated phenylalanine, the role of the aromatic amino acid in e.g. π-π-interactions can be studied by replacing Phe residues by Cha.

Cyclohexylamine, used as base for salt formation. The amino acid derivative is offered as cyclohexylammonium salt. Salts crystallize more readily than the free acid or they have to be generated as to obtain a shelf-stable product. Cyclohexylammonium salts are soluble in many organic solvents which facilitates liberation of the acid in a separate step or in situ.

L-α-Cyclohexylglycine is a non-polar, hindered amino acid. Chg is an important pharmaceutical intermediate, but it is found as well in natural products.

Chloroacetyl, a base-labile acyl group allowing further modifications of a peptide. The chlorine of N-chloroacyl-peptides can be replaced by nucleophiles as the Cys thiol moiety.

L-cis-Hydroxyproline, the stereoisomer of natural trans-hydroxyproline,  impedes collagen biosynthesis and deposition, but also the growth of pancreatic cancer cells.

Citrulline is a key intermadiate of the urea cycle. Additionally, Cit occurs in proteins due to a post-translational enzymatic modification of arginine residues.

CMC documentation includes all documents related to all aspects of the chemistry, manufacturing and control of drug substances and drug product.

C-type natriuretic peptide is a peptide produced mainly by the vascular endothelium with vasodilative properties. It shares structural and physiological properties with the atrial and brain natriuretic peptides (ANP and BNP).

Cyclopentyglycine is a non-polar, hindered amino acid. Cpg is an important pharmaceutical intermediate.

Corticotropin-releasing factor (CRF, CRH, corticorelin) is a hypothalamic hormone that is involved in stress response. It is secreted by the paraventricular nucleus (PVN) of the hypothalamus and stimulates the release of adrenocorticotropic hormone from the pituitary gland.

L-α,γ-Diaminobutyric acid, an α,ω-diamino acid, shorter homolog of Orn and Lys. By choosing a suitably protected derivative α,ω-diamino acids can be selectively Nω-modified or introduced for generating branched peptides or dendrimers.

4-(4-Dimethylaminophenylazo)-benzoyl, a chromphor linked to amino groups, used as a quencher in combination, e.g. with EDANS. Excitation of DABCYL at ca. 454 nm.

A chromophore linked to amino groups used as a quencher in combination, e.g. with EDANS. Excitation of Dabsyl at ca.436 nm.

5-Dimethylamino-1-naphthalene-sulfonyl, a fluorophor linked to amino groups, excitation at 342 nm, emission at 562 nm.

L-α,β-Diaminopropionic acid (Dap or Dpr), an α,ω-diamino acid, shorter homolog of Dab, Orn and Lys. By choosing a suitably protected derivative α,ω-diamino acids can be selectively Nω-modified or introduced for generating branched peptides or dendrimers.

Dicyclohexylamine. The amino acid derivative is offered as the salt formed with dicyclohexylamine, a sterically hindered secondary amine. Salts crystallize more readily than the free acid or they have to be generated as to obtain a shelf-stable product. Dicyclohexylammonium salts are soluble in many organic solvents which facilitates liberation of the acid in a separate step or in situ.

Dichlormethane

1-(4,4-Dimethyl-2,6-dioxocyclohex- 1-ylidene)ethyl (Dde), an amino-protecting group cleavad by 2% hydrazine hydrate in DMF. Nω-Dde can be selectively removed after Fmoc-SPPS from Dap, Dab Orn, or Lys allowing on-resin modification of the Nω-amino group.

See also ivDde and Dmab.

Diethylamine. The amino acid derivative is offered as the salt formed with diethylamine. Salts crystallize more readily than the free acid or they have to be generated as to obtain a shelf-stable product. Diethylammonium salts are soluble in many polar organic solvents which facilitates liberation of the acid in a separate step or in situ.

2,4-Dimethoxybenzyl, acid-labile carboxamide protecting group used for the reversible backbone modification of peptides. Incorporation of Fmoc-Dmb amino acids  or dipeptides (Fmoc-Xaa-DmbYaa-OH) during Fmoc-SPPS prevents aggregation and thus facilitates the elongation of the peptide. Facilitation of cyclization reactions and prevention of aspartimide formation are further applications of Dmb backbone protection.

Unlike Hmb amino acids/dipeptides, Dmb derivatives cannot form benzo-oxazepinones during activation.

1. N,N-Dimethylformamide
2. Drug Master File

 

Dimethylsulfoxide

2,4-Dinitrophenyl, a chromophor linked to amino groups. Often used as quencher in FRET substrates.

4,4′-Dimethoxydityl or bis-(4-methoxyphenyl)methyl, an acid-labile carboxamide protecting group compatible with Fmoc-SPPS.

(4,7,10-Tricarboxymethyl-1,4,7,10- tetraaza-cyclododecan-1-yl)-acetic acid, a cyclic chelator usually coupled to the N-terminus. DOTA allows labeling peptides with radionuclides as 68Ga or 90Y.

Diphenylmethyl (dityl), an acid-labile N-, O-, and S-protecting group.

Delta-sleep inducing peptide (DSIP) is found in neurons, peripheral organs, and plasma. DSIP was shown to induce mainly delta-sleep in rabbits, rats, mice, and humans. The peptide has been observed to affect electrophysiological activity, neurotransmitter levels in the brain. DSIP has been used to reduce withdrawal symptoms in alcoholic and opiate addicts and as an analgetic in chronic pain.

5-[(2-Aminoethyl)amino]naphthalene-1-sulfonic acid, a fluorophor usually coupled to the Nω of a diamino acid (e.g. Lys). EDANS is often used in FRET substrates in combination with e.g. DABCYL. Excitation at 340 nm, emission at 490 nm.

N-(2,4-Dinitrophenyl)-ethylene diamine, a chromophor usually coupled to the C-terminus. EDDnp is incorporated as a quencher in FRET substrates.

Ethylenediaminetetraacetic acid, a highly effective chelating agent for di- and trivalent metal ions.

Epidermal growth factor (EGF) exerts a wide variety of biological effects and plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR.

Enzyme immunoassay

Enzyme-linked immunosorbent assay

Endothelial monocyte-activating polypeptide, a cytokine.

Ethyl, an alkyl group, homolog of methyl (Me). N- and S-ethylation are permanent modifications of peptides.

Endothelins are vasoconstricting peptides produced by vascular endothelial cells. The endothelin family consists of three members, endothelin-1; endothelin-2; and endothelin-3.

3-(2-Furyl)acryloyl (FA), an N-terminally introduced chromophore. Absorption of FA-substrates is usually measured at 345nm.

Fluorescein-6-carbonyl, a fluorophor linked to amino groups, excitation at 490 nm, emission at 520 nm.

Fluorescence-activated cell sorting

Fibroblast growth factors (FGF) are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.

Fluorescein isothiocyanate (FITC), a fluorophor, reacts with amino groups. A spacer (at least β-alanine) has to to inserted when tagging a peptide with FITC at its N-terminus. N-terminal Nα-FITC-labeled amino acids will be split off when the peptide is treated with acid.

Excitation 490 nm, emission 520 nm.

9-Fluorenylmethyl is a base-labile O- and S-protecting group.

9-Fluorenylmethyloxycarbonyl (Fmoc), a base-labile Nα-protecting group cleaved by secondary amines. Standard Fmoc-SPPS protocols use 20% piperidine in DMF or NMP for Fmoc removal.

Formyl, an indole protecting group used in Boc-SPPS. Trp(For) is cleaved by HF in the presence of a mercaptan or by bases as piperidine.

An acyl group often N-terminally introduced, formyl is more polar than acetyl (Ac). A permanent modification of a peptide.

Fluorescence Resonance Energy Transfer (FRET), the non-radiative transfer of energy from an excited fluorophor (donor) to a suitable acceptor (quencher). The transfer is influenced by the distance, the dipolar orientation, and the spectral overlap of the donor and acceptor moieties. In FRET substrates, fluorophor and quencher are linked tightly by a peptide chain. Enzymatic cleavage is accompanied by increasing fluorescence, as donor and acceptor are separated.

Galactose is a monosaccharide (sugar). Galactosylation (especially O-galactosylation at Ser and Thr) is an important post-translational modification of proteins.

Ser/Thr(Gal/GalNAc)-peptides are best obtained by Fmoc-SPPS, as the O-glycosyl bond is acid-labile.

Growth hormone (GH) is a protein hormone that is synthesized and secreted by the somatotroph cells in the anterior pituitary. GH is involved in the control of several complex physiological processes, including growth and metabolism.

Gastric inhibitory polypeptide (also known as glucose-dependent insulinotropic peptide, GIP) is a member of the secretin family of hormones. GIP is a stimulator of insulin secretion and a an inhibitor of gastric acid secretion. It is also an essential regulator of insulin secretion and glucose homeostasis.

L-γ-Carboxyglutamic acid. Carboxylation of glutamic acid is a post-translational modification yielding Ca2+-binding proteins as osteocalcin.

Gla-containing peptides are best obtained by Fmoc-SPPS, as Gla tends to decarboxylate yielding Glu in the presence of strong acids.

Glucose, a monosaccharide (sugar). Glucosylation (O-glucosylation at Ser and Thr, N-glucosylation of Asn) is a common post-translational modification of proteins.

Ser/Thr(Glc/GlcNAc)-peptides are best obtained by Fmoc-SPPS, as the O-glycosyl bond is acid-labile.

Glucagon-like peptides belong to the glucagon superfamily of peptide hormones. They are derived from the C-terminal of proglucagon and are mainly produced by the intestinal L cells.

Granulocyte-macrophage-colony stimulating factor (GM-CSF) is a cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. GM-CSF is produced by various cell types in response to inflammatory mediators.

Gonadotropin-releasing hormone (also known as LHRH) is a decapeptide hormone which is synthesized in neurosecretory cells within the hypothalamus and released in a pulsatile fashion into the pituitary portal circulation. Pulsatile secretion is essential for reproductive functions, sexual development, and differentiation.

Growth hormone-releasing factor (growth hormone-releasing hormone, somatorelin) is a hypothalamic peptide hormone that acts on the pituitary gland and stimulates the release and synthesis of growth hormone.

Gastrin-releasing peptide (GRP) is a peptide hormone that elicits gastrin release and regulates gastric acid secretion and motor function.

L-cis-Hydroxyproline, the stereoisomer of natural trans-hydroxyproline, impedes collagen biosynthesis and deposition, but also the growth of pancreatic cancer cells.

Hepatitis B surface antigen

Hepatitis C virus

Human immunodeficiency virus

Human leukocyte antigen (HLA) system is the name of the human major histocompatibility complex.

2-Hydroxy-4-methoxybenzyl, acid-labile carboxamide protecting group used for the reversible backbone modification of peptides. Incorporation of Fmoc-Hmb amino acids  or dipeptides (Fmoc-Xaa-HmbYaa-OH) during Fmoc-SPPS prevents aggregation and thus facilitates the elongation of the peptide. Facilitation of cyclization reactions and prevention of aspartimide formation are further applications of Hmb backbone protection. See also Dmb.

L-Homoarginine, the homolog of L-arginine, also abbreviated Har, can be found in plasma and urine. Homoarginine results from the guanidination of Lys, which can also be performed on peptides and proteins.

Activated Har derivatives show a far lower tendency for lactamization than the corresponding Arg derivatives.

L-Homocitrulline, the homolog of L-citrulline, also abbreviated Hci, can be detected in human urine.

L-Homocysteine, the homolog of cysteine, also abbreviated Hcy, is generated by demethylation of methionine. Elevated Hcy levels in blood are a risk factor for cardiovascular and neurodegenerative diseases.

Contrary to Cys derivatives, Hcy derivatives do not tend to racemize during coupling nor to β-elimin.

L-Homoleucine, the homolog of L-leucine, also abbreviated Hle.

L-Homophenylalanine, the homolog of phenylalanine, also abbreviated Hph, is a constituent of ACE and renin inhibitors. Fmoc-Homophe-OH is a potential anti-inflammatory drug.

L-Homoproline or L-pipecolic acid, also abbreviated Pip or Hpr. The proline homolog Hpr is a degradation product of L-lysine. Both enantiomers can be detected in human plasma.

As proline residues strongly influence the conformation of a peptide, replacement of Pro by Hpr (or azetidine-2-carboxylic acid (Aze)) can modulate its secondary structure.

High-performance liquid chromatography (or high-pressure liquid chromatography, HPLC) is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.

Horseradish peroxidase

L-trans-Hydroxyproline is generated post-translationally by oxidation of proline. Hyp is a major constituent of collagen and mussel proteins.

O-protection of Hyp during Fmoc-SPPS is recommandable but not absolutely mandatory. The secondary hydroxyl function is somewhat more accessible than the Thr hydroxyl moiety.

Intercellular adhesion molecule, ICAMs belong to the immunoglobulin superfamily.

Interferons (IFNs) are proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions.

Immunoglobulins are multi-subunit proteins produced by the immune system. They are comprised of two heavy and two light chains with additional ancillary polypeptide chains depending on their isoforms. The immunoglobulins (Ig) can be divided into five different classes (IgA, IgD, IgE, IgG, and IgM) and various subclasses.

Insulin-like growth factors are polypeptides with high sequence similarity to insulin. The IGFs are part of a complex system involved in the regulation of cell growth and differentiation.

Immunohistochemistry

Interleukins belong to the cytokines and are soluble factors which stimulate growth-related activities of leukocytes as well as other cell types.

The IMPD is the European equivalent of the Investigational New Drug (IND) application in the US.

Current Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement. The IND is the means through which the sponsor technically obtains this exemption from the FDA.

Intraperitoneal

L-Isoserine, an isomer of L-serine, is a β-amino acid.

1-(4,4-Dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl (ivDde), an amino protecting group cleavad by 2% hydrazine hydrate in DMF. ivDde is more stable towards the repetitive piperidine treatments during Fmoc-SPPS than Dde. Nω-ivDde can be selectively removed from Dap, Dab Orn, or Lys allowing post-synthetic on-resin modification of the Nω-amino group.

Keyhole limpet hemocyanin (KLH) is a large, oxygen-carrying, multisubunit metalloprotein found in the hemolymph of the giant keyhole limpet. KLH is used as a carrier protein in the production of antibodies.

Luteinizing hormone-releasing hormone (LHRH or GnRH) is a decapeptide hormone which is synthesized in neurosecretory cells within the hypothalamus and released in a pulsatile fashion into the pituitary portal circulation. Pulsatile secretion is essential for reproductive functions, sexual development, and differentiation.

4-Methoxy-β-naphthylamide, also abbreviated MNA, is a fluorophore usually C-terminally attached to carboxypeptidase substrates. Excitation of the cleaved 4MβNA at 335-350 nm, emission at 410-440 nm.

4-Methoxybenzenesulfonyl (Mbs), a guanidino protecting group used in Boc-SPPS. Mbs is removed during HF cleavage.

4-Methylbenzyl, a sulfhydryl protecting group used in Boc-SPPS. Mbzl is more stable towards the repetitive TFA treatments than Mob, it is removed during HF cleavage.

(7-Methoxycoumarin-4-yl)acetic acid, a fluorophore which can be attached to amino groups. Mca is used in FRET substrates in combination with Dnp. Excitation 325 nm, emission 392 nm.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide first isolated from fish and rats. MCH is mainly involved in the regulation of skin pigmentation in teleosts and feeding behavior in mammals.

Monocyte chemotactic protein, a chemokine.

2-(Methyldiphenylsilyl)ethyl, a phosphate protecting group compatible with Fmoc-SPPS. MDPSE is cleaved by TFA.

Methyl, the simplest alkyl substituent. N-, O-, and S-Methylations constitute permanent modifications of peptides.

3-Methoxysuccinyl, which corresponds to deamino-Asp(OMe), a polar N-terminal blocking group often incorporated in carboxypeptidase substrates.

The major histocompatibility complex is the genetic region which contains the genes that encode MHC molecules. MHC molecules play an important role in the immune system and autoimmunity. In human beings the complex is also called the human leukocyte antigen (HLA) system.

4-Methoxybenzyl (Mob), an acid-labile S-protecting group used in Boc as well as in Fmoc-SPPS. Mob is removed by TFMSA and HF. The protecting group is often used in combination with Trt and Acm in the Fmoc-driven synthesis of peptides containing 3 disulfide bridges by consecutive bond formation.

Melanocyte-stimulating hormones are peptides that regulates skin color in humans and other vertebrates by stimulating the synthesis and distribution of melanin in melanocytes in mammals and melanophores in lower vertebrates.

4-Methoxy-2,3,6-trimethylbenzene-sulfonyl, a guanidino protecting group used in Fmoc-SPPS. Removal of Mtr from Arg requires somewhat harsher conditions, e.g. warming, than the standard acid-labile lateral protecting groups.

Mesitylene-2-sulfonyl (Mts) is used for protecting lateral guanidino, imidazole, and indole moieties. It is compatible with Boc-SPPS, though it is more acid-labile than Tos.

4-Methyltrityl (Mtt) is a highly acid-labile amino protecting group used in Fmoc-SPPS. The Mtt derivatives of Asn, Cys, Gln, and His are as well somewhat more acid-labile than the corresponding Trt derivatives.

L-β-(1-Naphthyl)alanine. 1-Nal and 2-Nal are non-polar aromatic amino acids related to phenylalaninne. They differ in the position, in which the naphthaline nucleus is substituted. Effects as π-π interactions may be changed when replacing Phe by 1-Nal.

L-β-(2-Naphthyl)alanine. 1-Nal and 2-Nal are non-polar aromatic amino acids related to phenylalaninne, differing in the position, in which the naphthaline nucleus is substituted. Effects as π-π interactions may be changed when replacing Phe by 2-Nal.

N-Ethylamide can be considered as a C-terminal decarboxy-alanine. In LHRH agonists as buserelin, NHEt mimics a C-terminal glycinamide.

Peptide N-ethylamides resist degradation by carboxypeptidases.

N-Methylamide. The N-methylated amide group is less polar than the amide, but it still can participate as a H-donor in hydrogen bonds.

N-t-Butylamide, a non-polar sterically demanding N-alkylated carboxamide.

L-Norleucine (Nle) is a stable isostere of L-methionine. If sulfoxide formation reduces the biological activity of a peptide, Nle can be inserted as a substitute for Met, usually without altering its behavior.

N,N-Dimethylamide. The bis-methylated carboxamide can participate only as acceptor in hydrogen bonds.

2-Nitrophenylsulfenyl (Nps) is an S-protecting group compatible with Boc-SPPS. As Nps is cleaved by thiols, it can be removed by a free sulfhydryl of Cys with concomitant disulfide formation.

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the brain. Together with the two gut hormones, pancreatic polypeptide (PP) and peptide YY (PYY) it belongs to the pancreatic polypeptide hormone family, also known as the neuropeptide Y family.

3-Nitro-2-pyridylsulfenyl is an S-protecting group compatible with Boc-SPPS. As Npys is cleaved by thiols, it can be removed by a free sulfhydryl of Cys with concomitant disulfide formation.

L-Norvaline, a non-polar aliphatic amino acid, homolog of Abu.

α-Naphthylamide is a fluorophore usually incorporated C-terminally into carboxypeptidase substrates. Excitation of the cleaved αNA at 330 nm, emission at 370 nm.

β-Naphthylamide is a fluorophore usually incorporated C-terminally into carboxypeptidase substrates. Excitation of the cleaved βNA at 320-340 nm, emission at 410-420 nm.

Allyl ester, a carboxy-protecting group compatible with Fmoc- and Boc-SPPS. As Aloc, the allyl ester is cleaved selectively by treatment with Pd(PPh3)4. Asp(OAll) is prone to base-catalyzed aspartimide formation during Fmoc-SPPS.

Benzyl ester, a carboxy protecting group used especially in solution synthesis. As Z, OBzl can be removed by catalytic hydrogenation (e.g. H2/Pd) or strong acids.

Cyclohexyl ester, OcHex is a standard carboxy-protecting group used in Boc-SPPS.

Cyclopentyl ester, a carboxy-protecting group used in Boc-SPPS. OcPent is cleaved by HF.

3,4-Dihydro-4-oxo-1,2,3-benzotriazine-3-yl esters of protected amino acids are highly reactive. Couplings using Fmoc-amino acid Dhbt esters (also called OOBt esters) can be monitored spectrophotometrically.

4-(N-[1(4,4-Dimethyl-2,6-dioxocyclohexylidene)-3-ethylbutyl]amino)benzyl ester (ODmab), carboxy-protecting group used in Fmoc-SPPS. ODmab is cleaved by 2% hydrazine hydrate in DMF.

See also Dde, ivDde.

The 2,4-dimethoxybenzyl ester is a highly acid-labile carboxy-protecting group removable with 1% TFA in methylene chloride.

Ethyl ester. As ethyl esters can only be cleaved under quite harsh conditions, they can be considered as a modification increasing the lipophilicity and the stability of a peptide.

9-Fluorenylmethyl ester, a base-labile carboxy-protecting group cleaved by piperidine in DMF.

Hexyl esters can only be cleaved under quite harsh conditions, they are introduced for increasing the lipophilicity and the stability of a peptide.

L-Octahydroindole-2-carboxylic acid (Oic) is a non-polar, hindered amino acid. Insertion of this proline-related amino acid strongly influences the conformation of a peptide.

Methyl esters constitute the simplest esters. Methyl esters play an important role as semi-permanent C-terminal protective groups in solution synthesis They can be converted into peptide hydrazides, precursors of the reactive peptide azides. Azide coupling still is the most popular fragment coupling method in the solution synthesis of peptides.

3-Methylpent-3-yl ester (OMpe), an acid-labile carboxy-protecting group used for Asp in  Fmoc-SPPS. This sterically more demanding analog of the t-butyl ester has been developed especially for reducing base-catalyzed aspartimide formation.

o-Nitrophenyl esters of Boc- or Z-amino acids are pre-activated derivatives used in the solution synthesis of peptides.

Pentachlorophenyl ester, an “active ester”.

Pentafluorophenyl esters of Fmoc amino acids are used as pre-activated dervatives especially in fully automated SPPS.

L-Ornithine (Orn) is generated from Arg during the urea cycle, but it can also be observed as an Arg degradation product in peptides. Orn formation via acylation of the Arg guanidino moiety is a well-known side-reaction in peptide synthesis.

N-Hydroxysuccinimide esters (OSu, also abbreviated as NHS) are well-established “active esters”, Even though more reactive pre-activated amino acid derivatives are available, OSu esters still are commonly used in peptide synthesis and, especially, in peptide modification. OSu esters are safe, sterically unhindered, compatible with aqueous systems, and convenient to handle.

t-Butyl ester, standard acid-labile carboxy protecting group used in Fmoc-SPPS as well as in solution synthesis.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a highly conserved neuropeptide that is widely expressed in the mammalian brain. PACAP acts by elevating intracellular cyclic AMP level via its interaction with its receptors.

PACAP is an important regulator of endocrine and homeostatic processes, such as secretion of pituitary and gut hormones and food intake.

Palmitoyl, a non-polar acyl group introduced N-terminally or laterally. Palmitoylation represents a permanent modification of a peptide, it is also observed as post-translational modification of proteins.

Phenylacetamidomethyl-resin is a resin developed specifically for Boc-SPPS. The peptide is obtained by cleavage with HF. The PAM anchor group is more stable towards the repetitive TFA treatments during Boc-SPPS than the benzyl linkage to Merrifield resin.

2,2,4,6,7-Pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), a standard guanidino protecting group used in Fmoc-SPPS, slightly more acid-labile than Pmc.

Phosphate buffered saline

L-Penicillamine, an analog of L-cysteine.

Whereas D-Penicillamine is a precursor of penicilline and used as a drug, the L-enantiomer is toxic. In peptides, Pen is incorporated as a Cys replacement in disulfide bridges.

Peptides and proteins are chains of α-amino acids linked in a defined order, they only differ in length. Both types of molecules are omnipresent in living organisms and essential for their functioning. Peptides consist of 2 amino acids at minimum, whereas proteins are assembled from at least 100 of these building blocks (the division is somewhat arbitrary). If not isolated from natural sources, peptides can be produced by chemical means, e.g., by SPPS, whereas proteins are usually produced by recombinant methods.

Phenylacetyl (Phenylac or Phac), an acyl group often N-terminally introduced, less polar than acetyl (Ac). A permanent modification of a peptide.

L-Phenylglycine (Phg), a metabolite observed in human urine and plasma, is used for obtaining β-lactam antibiotics.

Peptide Histidine Isoleucine (PHI), a porcine peptide related to VIP and secretin.

Peptide Histidine Methionine (PHM), a human peptide related to VIP.

2,2,5,7,8-Pentamethylchroman-6-sulfonyl (Pmc), a standard guanidino protecting group used in Fmoc-SPPS, slightly less acid-labile than Pbf.

p-Nitroanilide, a chromophore usually attached to the C-terminus of carboxypeptidase substrates. The absorption of the released p-nitroaniline is usually measured at 405 or 410 nm.

L-Propargylglycine (Pra) is produced by microorganisms. This amino acid containing a triple bond has gained much interest as a building block for obtaining  peptides which can participate in “click chemistry” reactions, e.g. with azides.

Parathyroid hormone (pTH) is a polypeptide hormone secreted by the parathyroid glands. pTH regulates calcium and phosphorus concentration in extracellular fluid.

L-Pyroglutamic acid is also abbreviated Pgl, Glp, pGlu, <Glu. Pyroglutamate formation from Gln is a common N-terminal modification of bioactive peptides increasing their metabolic stability.

4-Phenylazobenzyloxycarbonyl, a chromophoric N-protecting group cleaved by catalytic hydrogenation or strong acids, absorption maxima at 229, 320 and 441 nm.

Recombinant

Radioimmunoassay

Sarcosine, the simplest N-alkylated amino acid, is ubiquitous in biological material.

Thiobenzyl ester. Peptide C-terminal thioesters are used as carboxypeptidase substrates.

Ethylthio, an S-protecting group cleavable by reduction with phosphines.

Solid-phase peptide synthesis, the standard method for obtaining peptides. The peptide, linked by its C-terminus to a carrier, an inert, insoluble but swellable polymer, is elongated stepwise. The method can be fully automated. Fmoc- and Boc-SPPS differ in the choice of the temporary (= Boc or Fmoc) and permanent (side-chain) protecting groups. The type of Nα-blocking group determines the options for side-chain protection and the conditions of final cleavage (removal of the permanent protective groups and splitting from the carrier). Fmoc-SPPS is considered the milder method.

Statine, a γ-amino acid, is a constituent of the naturally occurring enzyme inhibitor pepstatin and synthetic renin inhibitors.

t-Butylthio (StBu), an S-protecting group cleavable by reduction with phosphines, compatible with Boc-SPPS.

Succinyl, a polar N-terminal modification corresponding to deamino-Asp. Often incorporated in carboxypeptidase substrates.

Carboxytetramethylrhodamine (TAMRA or TMR), a fluorophore, which can be attached to amino groups. TAMRA is used in FRET substrates in combination with FAM. Excitation at 485 nm, emission at 535 nm.

t-Butyl, a bulky alkyl substituent and a standard acid-labile protecting group for alcohols and phenols, cleaved by TFA.

Triethylammonium phosphate is a possible buffer used in the mobile phase of reversed phase HPLC.

Trifluoroacetic acid (TFA) is a rather strong acid. TFA used for the final cleavage in Fmoc-SPPS and for the removal of tBu-derived protecting groups.

Trifluoroacetyl is employed as a base-labile amino-protecting group. As it is removed under relatively harsh coditions, e.g. with sodium borohydride, it can also be introduced as modification.

Trifluoromethanesulfonic acid (TFMSA) is a stronger acid than TFA. TFMSA solutions in TFA can replace the highly toxic hydrogen fluoride in the final cleavage during Boc-SPPS.

Transforming growth factors are polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells.

Tetrahydrofuran

L-Thiazolidine-4-carboxylic acid (Thz) is obtained by treatment of cysteine with formaladehyde Thz formation has also been observed as a side reaction of N-terminal Cys. The Pro analog has gained importance as a masked Cys in native chemical ligation.

L-1,2,3,4-Tetrahydroisoquinoline- 3-carboxylic acid, a constrained analog of phenylalanine.

Even though it is a semi-quantitative method, thin layer chromatography (TLC) is especially suitable for analyzing amino acid derivatives. TLC is a remarkably versatile analytical tool due to the large choice of elution systems and plate development methods, which can be optimized for each individual product and/or the detection of traces of its possible contaminants (e.g. unreacted educts). Contrary to column chromatography, a number of samples can be run side by side on a TLC plate, which allows for a better comparison.

L-tert-Leucine (Tle), a non-polar amino acid with a sterically demanding side chain, which destabilizes α-helices.

Trademark

2,4,6-Trimethoxybenzyl, an acid-labile Asn and Gln amide protecting group used in Fmoc-SPPS.

Tumor necrosis factor is a multifunctional cytokine that is produced mainly by macrophages. It is involved in the regulation of immunity and inflammation and is a modulator of cellular growth and differentiation.

Trishydroxymethylnitromethane (which is ketalized with cyclohexanone) represents a lateral amino protecting group, which is removed in two steps. Acidolytic cleavage after Fmoc-SPPS leaves the amino group protected as monocarbamate of tris-hydroxymethyl-nitromethane, which is removed under slightly basic conditions.

Tosyl (p-toluenesulfonyl) serves as standard guanidino and imidazole protecting group used in Boc-SPPS. Tos can also be introduced as a permanent modification, e.g. for blocking the N-terminus.

Trityl (triphenylmethyl) is a standard acid-labile protecting group for  Asn, Cys, Gln, and His used in Fmoc-SPPS. See also Mtt.

US Pharmacopeia

Vascular Cell Adhesion Molecule

Vasoactive intestinal contractor (VIC) has been described recently to be the rat form of endothelin-2 (ET-2).

Vasoactive intestinal peptide (VIP) is 28 amino acid peptide belonging to the glucagon-growth hormone-releasing factor-secretin superfamily of peptides. VIP is a multi-functional neuropeptide with physiological effects including vasodilation, bronchodilation, immunosuppression, hormonal secretion and increases in gastric motility.

9-Xanthhydryl, an acid-labile amide protecting group used in Boc-SPPS for Asn and Gln. As Xan can be cleaved by TFA, its main purpose is to protect the lateral amide function during activation and coupling.

Benzyloxycarbonyl, a most important amino protecting group in peptide synthesis as well as in organic chemistry, is usually abbreviated Z or Cbz. A standard temporary amino protecting group in solution synthesis. Z is cleaved by hydrogenolysis or strong acids as neat HF or HBr/acetic acid. Halogenation of the aromatic nucleus generates more acid-stabile protective groups as 2-chloro-Z, whereas p- and o-methoxy groups render it more acid-labile.