Bachem offers complimentary white papers on innovative products, services or processes in peptide and oligonucleotide research, as well as technical information on peptide synthesis.
Extracellular amyloid-β peptide deposition into cerebellar plaques and formation of intracellular neurofibrillary fibers accompanied by the loss of neurons are characteristic histopathological lesions found in the brains of Alzheimer‘s disease patients. Individuals suffering from this disease show a gradual loss of cognitive functions and disturbances in behavior. Apart from some rare familial forms of the disease, the onset of Alzheimer‘s disease is usually above 60 years. Since the risk to develop the disease increases with age, Alzheimer‘s disease has turned into a major health and social problem in “first world” countries with an increasing proportion of older people, and is going to become one in emerging states. In this brochure we present amyloid peptides and related products for Alzheimer‘s disease research.
A New Turn in Peptide Purification
Nowadays, solid phase peptide synthesis (SPPS) is the go-to method for peptide synthesis. It is a rapid, orthogonal and efficient process. SPPS is able to synthesize sets of peptides in parallel, while the go-to purification method, RP-HPLC, is a linear process and can represent the bottleneck of peptide development and manufacturing. The new and innovative purification method introduced in this whitepaper extends the previous features of SPPS to the purification of peptides. The catch-and-release platform, termed Peptide Easy Clean, developed by Belyntic in collaboration with Bachem, enables the successful and innovative purification of peptides.
Ribosomally synthesized antimicrobial peptides (AMPs) constitute a structurally diverse group of molecules found virtually in all organisms. Most antimicrobial peptides contain less than 100 amino acid residues, have a net positive charge, and are membrane active. They are major players in the innate immune defense but can also have roles in processes as chemokine induction, chemotaxis, inflammation, and wound healing. In addition to their antimicrobial effects, many of them show antiviral and antineoplastic activities.
Cell-penetrating peptides (CPPs) constitute a promising tool for the cellular import of drug cargos. They have been successfully applied for in vitro and in vivo delivery of a variety of therapeutic molecules including plasmids, DNA, oligonucleotides, siRNA, PNA, proteins, peptides, low molecular weight drugs, liposomes, and nanoparticles.
Bachem highlights the importance of “click reactions” in peptide chemistry as a simple and versatile concept for peptide synthesis and chemoselective modification. The broad spectrum of applications of the reaction includes ligation, cyclization, bio-conjugation, and radiolabeling of peptides.
Peptides are involved in many physiological processes. Their broad acceptance as natural molecules, relatively high stability and well defined actions have made them attractive for many skin-related indications, most notably in anti-aging therapy. The aging population and their prevalent wish to keep a young and healthy appearance have substantially driven the development of anti-aging products. Many peptides marketed in cosmetic products are advertised to slow down or even reverse the aging process of the skin. Common modes of action include stimulation of collagen synthesis and inhibition of neurotransmitter release in order to reduce fine lines and wrinkles caused by the repetitive muscular activities of facial expression. We have considerable expertise and long-standing experience in peptide synthesis. With our capacity to upscale the production of simple and modified peptides, we are the partner of choice for the pharmaceutical and cosmetic industries.
Cystine disulfide bridges help to stabilize the biologically active conformation of peptides and proteins. They are generated by incorporation of cysteine residues followed by oxidation of the thiol functions yielding disulfides („folding“). For the chemical synthesis of peptides, a range of protecting groups has been developed for blocking these sensitive moieties which may be removed either directly before or during oxidative folding. When synthesizing peptides containing two or more disulfide bonds, S-protection may have to be varied to allow consecutive bridge formation for obtaining an unambiguous structure.
In 2014, according to data from the WHO, 422 million adults (or 8.5% of the population) had diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, compared with 108 million (4.7%) in 1980. Diabetes mellitus can be divided into two main types, type 1 or insulin-dependent diabetes mellitus (IDDM) and type 2, or non insulin-dependent diabetes mellitus (NIDDM). The absolute lack of insulin, due to destruction of the insulin producing pancreatic β-cells, is the particular disorder in type 1 diabetes. Type 2 diabetes is mainly characterized by the inability of cells to respond to insulin. The condition affects mostly the cells of muscle and fat tissue, and results in a condition known as „insulin resistance“.
Fluorescence Resonance Energy Transfer (FRET) is the non-radiative transfer of energy from an excited fluorophore (or donor) to a suitable quencher (or acceptor) molecule. FRET is used in a variety of applications including the measurement of protease activity with substrates, in which the fluorophore is separated from the quencher by a short peptide sequence containing the enzyme cleavage site. Proteolysis of the peptide results in fluorescence as the fluorophore and quencher are separated. In this brochure we present a range of highly sensitive FRET protease substrates for a variety of enzymes.
Microspheres and Nanoparticles for Peptide Delivery
Delivery of peptides is a challenging task due to their poor stability toward proteolytic enzymes, their large size and poor penetration into cells. The great innovation in this field relies on the formulation of microspheres and nanoparticles to encapsulate the peptide in order to enhance its bioavailability and therapeutic efficacy. To discover more on how Bachem is part of this technology in achieving successful formulation of APIs, please read our whitepaper on the benefits and challenges of microspheres and nanoparticles for peptide delivery.
Peptides in Cancer Research
This brochure discusses the potential use of peptides as anticancer drugs highlighting current scenario and future prospects. Some peptides are also used as diagnostic tools for cancer detection. G-protein-coupled receptors are most important targets in drug development. Many of them are overexpressed in tumor cells. Amongst them, the GnRH receptor is the target of a considerable number of GnRH agonists and antagonists used in cancer management. GnRH (gonadotropin-releasing hormone) or LHRH (luteinizing hormone-releasing hormone) is a decapeptide produced in in the hypothalamus and released in a pulsatile fashion into the pituitary portal circulation. Prolonged non-pulsatile administration of LHRH leads to downregulation of LH and FSH secretion, followed by a suppression of gonadal steroid synthesis. For this reason, longer-acting GnRH agonists as well as antagonists are used for the treatment of hormone-dependent breast and prostate cancers. Most neuroendocrine tumors show a marked overexpression of somatostatin receptors, especially of sst2, which instigated the development of somatostatin agonists as octreotide. These compounds also play an important role in diagnosis. Bombesin/gastrin-releasing peptide receptors can be overexpressed in malignant cells. Antagonists of these peptides inhibit tumor growth. Active immunization by peptide vaccines is another promising strategy to fight cancer.
Pseudoproline Dipeptides and Isoacyl Dipeptides
The synthesis of very long peptides and “difficult sequences” by chemical means still poses a challenge to the peptide chemist. The difficulties encountered during such syntheses usually are due to the aggregation of the resin-bound peptide. Proline residues disrupt such ordered structures efficiently. Temporary Pro mimics can be readily obtained from Ser and Thr by oxazolidine or from Cys by thiazolidine (“pseudoproline”) formation. Both 2,2-dimethyloxazolidines and -thiazolidines are smoothly cleaved by trifluoroacetic acid and thus suitable for Fmoc-SPPS. Disruption of Ser- and / or Thr-containing aggregates is achieved as well by introducing depsipeptide (“O-acyl isopeptide”) bonds into the peptide backbone. The resulting isopeptide is rearranged yielding the desired sequence in slightly basic solution.
Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) belong to a family of regulatory peptides which are widely expressed in the body. Their widespread distribution is correlated with their involvement in a large variety of biological activities. Both peptides display a remarkable amino acid sequence homology. They exert their biological effects through specific membrane receptors, belonging to the superfamily of G-protein-coupled receptors (GPCRs), named PACAP/VIP-receptors, whose signaling mechanism involves the activation of adenylate cyclase and phospholipase C cascades. Since their discovery VIP and PACAP have become the research interest of many laboratories, as reflected by the increasing number of publications related to this subject. In this brochure we present a selection of products for VIP and PACAP research.
Bachem offers a choice of generic peptides for use as active ingredients in veterinary medicine, amongst them gonadorelin and gonadorelin agonists and antagonists. For a compilation of our peptide APIs please see page 20. Our offer is complemented by the corresponding peptides in research quality to be found on page 23-25. Additionally, we provide the anesthetics etomidate and propofol as non-peptide generic APIs for the veterinary practice, please see page 21.