Which analytical data do you provide for your amino acid derivatives?
The range of analytical data listed on the ADS depends on the type of product, as methods for analyzing amino acid derivatives (and very short peptides), peptides, and “non-peptidic” compounds differ somewhat.
An ADS (Analytical Datasheet) issued for an amino acid derivative can list:
- Lot number
- Type of product: catalog or custom-synthesized
- Product number
- Product designation
- Molecular formula
- Relative molecular mass
- Tests performed
- Appearance
- Appearance of solution, solvent
- Molecular mass, obtained by mass spectrometry
- Elemental analysis
- Purity (determined by TLC), TLC conditions
- Optical rotation
- Melting Point
- Water content
- Substitution (loaded resins)
How can you be sure that the derivative is optically pure?
Certain reactions involving α-amino acids carry the risk of concomitant racemization, especially when the α-carboxy group has to be activated in the presence of bases. So a synthetic strategy avoiding racemization-prone conversions has to be developed.
If the risk of racemization exists (e.g. during loading of resins), the optical purity is controlled after performing the reaction.
The optical rotation is determined only if reference values can be taken from the literature.
Which base resins do you use for obtaining loaded resins for SPPS?
Wang resin (4-alkoxybenzyl alcohol resin), SASRIN (2-methoxy-4-alkoxybenzyl alcohol resin), 2-chlorotrityl resin (Fmoc)
Merrifield resin (chloromethyl resin), PAM (phenylacetamidomethyl) resin (Boc)
All our resins are based on polystyrene cross-linked with 1% divinylbenzene.
We offer resin derivatives in two particle sizes, 200-400 mesh and 100-200 mesh.
Which resins can be used for Fmoc-SPPS ?
Resins suitable for the Fmoc-SPPS of “peptide acids” (i.e. C-terminal carboxyl group):
Wang resin (4-alkoxybenzyl alcohol resin), SASRIN (2-methoxy-4-alkoxybenzyl alcohol resin), 2-chlorotrityl chloride resin.
As esterification of the C-terminal Fmoc-amino acid can be accompanied by concomitant racemization, we recommend using preloaded resins. They are produced under conditions optimized for minimal racemization and tested for chiral purity.
Resins suitable for the Fmoc-SPPS of peptide amides:
Fmoc-Rink amide AM resin (Fmoc-2,4-dimethoxy-4'-(carboxymethyloxy)-benzhydrylamine linked to Aminomethyl resin), Tricyclic amide linker resin, PAL resin (4-Alkoxy-2,6-dimethoxybenzylamine resin), Xanthenyl linker resin (Sieber amide resin). As removal of Fmoc and loading of the C-terminal amino acid can be easily included in standard Fmoc-SPPS protocols, we do not offer preloaded amide resins.
Which amino acid derivatives can be used for Fmoc-SPPS?
The side-chain protecting groups have to withstand repetitive treatments with piperidine.
Derivatives of trifunctional amino acids used in "standard" Fmoc-SPPS:
Fmoc-Arg(Pbf)-OH, Fmoc-Arg(Pmc)-OH
Fmoc-Asp(OtBu)-OH
Fmoc-Asn(Trt)-OH, Fmoc-Asn(Mtt)-OH (for N-terminal Asn)
Fmoc-Cys(Trt)-OH (single S-S-bridge, or "folding")
Fmoc-Gln(Trt)-OH
Fmoc-Glu(OtBu)-OH
Fmoc-His(1-Trt)-OH (Fmoc-His(Trt)-OH)
Fmoc-Lys(Boc)-OH
Fmoc-Ser(tBu)-OH
Fmoc-Thr(tBu)-OH
Fmoc-Trp(Boc)-OH
Fmoc-Tyr(tBu)-OH
All lateral protecting groups can be removed with TFA.
Which resins can be used for Boc-SPPS?
Resins suitable for the Boc-SPPS of “peptide acids” (i.e. C-terminal carboxyl group):
Merrifield resin (chloromethyl resin) and hydroxymethyl resin, PAM (phenylacetamidomethyl) resin (only available in preloaded form)
As esterification of the C-terminal Boc-amino acid can be accompanied by concomitant racemization, we recommend using preloaded resins. They are produced under conditions optimized for minimal racemization and tested for optical purity.
Resins suitable for the Boc-SPPS of peptide amides:
MBHA resin (4-methyl-benzhydrylamine resin), BHA resin (benzhydrylamine resin)
Both resins are offered as hydrochlorides, the amino group has to be liberated before coupling the C-terminal Boc-amino acid.
As the loading step can be easily included in standard Boc-SPPS protocols, we do not offer preloaded amide resins.
Which amino acid derivatives can be used for Boc-SPPS?
The side-chain protecting groups have to withstand repetitive treatment with trifluoroacetic acid in methylene chloride.
Derivatives of trifunctional amino acids for "standard" Boc-SPPS:
Boc-Arg(Tos)-OH
Boc-Asp(OcHex)-OH
Boc-Asn(Xan)-OH
Boc-Cys(Mob)-OH, Boc-Cys(MBzl)-OH
Boc-Gln(Xan)-OH
Boc-Glu(OcHex)-OH
Boc-His(Tos)-OH
Boc-Lys(2-chloro-Z)-OH
Boc-Ser(Bzl)-OH
Boc-Thr(Bzl)-OH
Boc-Trp-OH, Boc-Trp(For)-OH
Boc-Tyr(2-bromo-Bzl)-OH, Boc-Tyr(2,6-dichloro-Bzl)-OH
All lateral protecting groups can be removed with HF (removal of For only in the presence of a thiol)
Which resins can be used for the synthesis of peptide acids?
Resins suitable for Fmoc-SPPS:
Wang resin (4-alkoxybenzyl alcohol resin), SASRIN (2-methoxy-4-alkoxybenzyl alcohol resin), 2-chlorotrityl chloride resin.
Resins suitable for Boc-SPPS:
Merrifield resin (chloromethyl resin) and hydroxymethyl resin, PAM (phenylacetamidomethyl) resin (only available in preloaded form)
As esterification of the C-terminal amino acid can be accompanied by concomitant racemization, we recommend using preloaded resins. They are produced under conditions optimized for minimal racemization and tested for optical purity.
How to avoid problems with a C-terminal proline during Boc-SPPS?
Diketopiperazine formation may occur after deblocking the second amino acid, the penultimate residue of the peptide to be synthesized, especially in case of a C-terminal proline (generally: in case of Nα-alkylated amino acids). Losses due to this reaction resulting in premature cleavage from the resin can be considerably reduced by simultaneous coupling and liberation of the amino group from the trifluoroacetate.
Why use Pro-chlorotrityl resin for obtaining peptides with C-terminal Pro?
Diketopiperazine formation may occur after deblocking the second amino acid, especially in case of a C-terminal proline (generally: in case of Nα-alkylated amino acids). The bulky chlorotrityl group prevents this cyclization resulting in premature cleavage.
Fmoc-Pro-DHPP-® (D-1830) represents a more acid-stable alternative to 2-chlorotrityl resin.
Which resins can be used for the synthesis of peptide amides?
Resins suitable for the Fmoc-SPPS of peptide amides:
Fmoc-Rink amide AM resin (Fmoc-2,4-dimethoxy-4'-(carboxymethyloxy)-benzhydrylamine linked to Aminomethyl resin), Tricyclic amide linker resin, PAL resin, Xanthenyl linker resin (Sieber amide resin).
Resins suitable for the Boc-SPPS of peptide amides:
4-Methyl-benzhydrylamine resin (MBHA resin), benzhydrylamine resin (BHA resin)
Both are offered as hydrochlorides, the amino group has to be liberated before coupling the C-terminal Boc-amino acid.
Which resins allow obtaining fully protected peptides?
Resins suitable for Fmoc-SPPS of protected peptides:
SASRIN (2-methoxy-4-alkoxybenzyl alcohol resin) and 2-Chlorotrityl resin
Xanthenyl linker resin (for protected peptide amides)
SASRIN-carbazate (for protected peptide hydrazides)
Bachem does not offer resins specifically designed for the Boc-SPPS of protected peptides. Such peptides can also be obtained by Boc-SPPS on e.g. Merrifield resin followed by cleavage with nucleophiles.
Do you offer resins suitable for the synthesis of peptide alcohols?
Yes, we do.
2-Chlorotrityl resin has been used for the Fmoc-SPPS of peptide alcohols.
Diphenyldiazomethane resin (PDDM resin) can be used as a carrier for the Fmoc-SPPS of peptides, but it is especially suitable for the synthesis of peptide alcohols, which may also be obtained in protected form.
Bachem also offers Ellman's dihydropyrane resin.
Why are certain amino acid derivatives sold as salts?
Amino acid derivatives have to be sufficiently shelf-stable and preferably crystalline to be marketed.
In most cases, lack of crystallinity is the reason for converting amino acid derivatives into DCHA, DEA, or CHA salts. N-protected Amino acid derivatives carrying very acid-labile protecting groups are offered as salts as to avoid premature cleavage during storage (e.g. Bpoc-Gly-OH · DCHA). For a protocol describing the liberation of the acid please see the Technical Note downloadable from our website.
Esters of amino acids have to be converted into salts of strong acids as to prevent oligomerization (e.g. H-Ala-OMe · HCl).
Do you offer cold isotope labeled amino acid derivatives?
Yes, we offer a number of 2H (deuterated)- and 15N-labeled derivatives.
You will find two families, one containing our 15N-labeled derivatives and the other consisting of our deuterated derivatives, in the amino acids section of our online catalog.
Do you offer spacers?
Spacers which can be incorporated during Fmoc-SPPS:
Fmoc-εAhx-OH, Fmoc-8-aminooctanoic acid (Fmoc-8-Aoc-OH) (both non-polar)
Fmoc-AEEAc-OH (polar)
For Boc-SPPS:
Boc-εAhx-OH, 11-(Boc-amino)-undecanoic acid
N-terminal FITC requires a spacer.
