Search

Melanocortins are peptides that share a common central pharmacophor. Melanin pigmentation of interfollicular epidermis and hair via MC1R remains the key physiologic function of the naturally occurring melanocortin peptides in skin. Moreover, the melanocortins are crucially involved in the ultraviolet light-induced tanning response. Under pathophysiologic conditions, melanocortin peptides induce cutaneous hyperpigmentation, likewise via the MC1R axis, e.g. in patients with Addison's disease, ectopic precursor pro-opiomelanocortin (POMC) syndrome and in those with abnormally elevated melanocortin blood levels. Translational research on α‑MSH (melanocyte-stimulating hormones) and their antagonists has further revealed a variety of other biological activities beyond pigmentation. They include cytoprotection, antioxidative effects, regulation of collagen metabolism and fibrosis, sebum production, and cutaneous wound healing. These findings have also promoted the development of novel therapies in clinical dermatology including the exploitation of afamelanotide. In 2015, this agent became the first in-class synthetic α‑MSH analogue to be approved in dermatology for the treatment of erythropoetic protoporphyria. In addition to afamelanotide, setmelanotide has recently emerged as a highly selective MC4R agonist useful for the treatment of distinct forms of genetically determined obesity, e.g., POMC deficiency. Future perspectives in dermatology reside in treatment of other difficult-to-treat skin diseases with α‑MSH analogues, either with topical or systemic formulations. Moreover, synthetic melanocortin peptide derivatives lacking the central pharmacophor but with maintained anti-inflammatory effects could become a promising strategy for the design of new therapies in dermatology.

The chalcogen elements oxygen, sulfur, and selenium are essential constituents of side chain functions of natural amino acids. Conversely, no structural and biological function has been discovered so far for the heavier and more metallic tellurium element. In the methionine series, only the sulfur-containing methionine is a proteinogenic amino acid, while selenomethionine and telluromethionine are natural amino acids that are incorporated into proteins most probably because of the tolerance of the methionyl-tRNA synthetase; so far, methoxinine the oxygen analogue has not been discovered in natural compounds. Similarly, the chalcogen analogues of tryptophan and phenylalanine in which the benzene ring has been replaced by the largely isosteric thiophene, selenophene, and more recently, even tellurophene are fully synthetic mimics that are incorporated with more or less efficiency into proteins via the related tryptophanyl- and phenylalanyl-tRNA synthetases, respectively. In the serine/cysteine series, also selenocysteine is a proteinogenic amino acid that is inserted into proteins by a special translation mechanism, while the tellurocysteine is again most probably incorporated into proteins by the tolerance of the cysteinyl-tRNA synthetase. For research purposes, all of these natural and synthetic chalcogen amino acids have been extensively applied in peptide and protein research to exploit their different physicochemical properties for modulating structural and functional properties in synthetic peptides and rDNA expressed proteins as discussed in the following review., (© 2019 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)

The incretin hormone glucagon-like peptide 1 (GLP-1) is being synthesized from L-cells in the gut and enhances glucose-induced insulin secretion. Metabolic control of type 2 diabetic patients can be markedly improved by additional administration of GLP-1, however, this peptide is almost immediately degraded and therefore has little clinical value. The synthetic GLP-1 agonist exenatide underlies a different metabolism and has recently been approved by the U.S. Food and Drug Administration for the adjunctive treatment of patients with type 2 diabetes who are suboptimally controlled with metformin and/or sulfonylurea. First controlled clinical trials provided evidence that glycaemic control under exenatide administered twice daily in a dose of 5-10 microg was not inferior to conventional insulin therapy. Novel aspects in the treatment of type 2 diabetes by GLP-1 receptor stimulation further include its influence on the insulin secretory pattern, insulin/glucagon ratio, body weight and possibly even pancreatic beta cell mass. However, a general application of exenatide in the treatment of type 2 diabetes will also largely depend on the therapy behavior of patients, a possible immunogenicity and the rate of adverse events. Furthermore, a possible indication for exenatide as first-line therapy of type 2 diabetes and the prognostic relevance of this novel therapeutic approach have yet to be defined.

Antibodies against citrullinated peptides are highly specific for rheumatoid arthritis. With second generation ELISA-kits, CCP-antibodies have a specificity of > 96 % and a sensitivity of 68 %. CCP-antibodies can be detected several years before the onset of clinical symptoms. They are, thus, ideally suited for the differential diagnosis between early forms of rheumatoid arthritis and other inflammatory arthritides. As CCP-antibodies are associated with aggressive and treatment resistant courses of rheumatoid arthritis, their high predictive value can be useful in therapeutic strategy decisions in order to verify early treatment with disease modifying drugs or biologicals in line with modern treatment approaches to start aggressive therapy early to prevent bone erosions. In contrast to their role in differential diagnosis and prediction of aggressive disease, however, CCP-antibodies are of no value in monitoring treatment as they do not change essentially over prolonged periods of time.

The present report gives a review about the localization, release and gastrointestinal actions of peptide YY in different animal species and in humans. Possible mechanisms of action, the physiological and pathophysiological significance of peptide YY and the role of peptide YY 3-36 are discussed. Finally, unanswered questions are specified.

The application of polymer supports for the synthesis of polypeptides, oligonucleotides, and oligosaccharides is presented in this article and discussed in view of their methodology. The fundamentals of the polymer-supported synthesis are described as well as the role of the polymer supports in the synthetic cycle, and the problems associated are debated. It is focused on typical polymer supports for each substance class, and an overview is given on recent tendencies of development in the polymer-supported methods of synthesis.

A novel side reaction in Fmoc-solid-phase synthesis, which occurs during removal of protecting groups and detachment from the resin, was elucidated by investigations on model peptides: During the cleavage of Pmc- or Mtr-protecting groups from arginine residues by trifluoroacetic acid in peptides with O-tert-butyl-protected aliphatic hydroxyamino acids, peptides containing O3-sulfo-serine and O3-sulfo-threonine are formed as side-products in high yields, if suitable scavengers are absent. Subsequent to their isolation and purification, the structures of these peptide sulfuric acid mono-esters could unequivocally be proven by chemical and spectroscopic (MS, NMR, IR) methods.

The gonadotropin-releasing-hormone analogue D-Phe6-GnRH was complexed with polyglycine under non-denaturing conditions. The liberation behaviour of these complexes was investigated in vitro in dependence of hormone content. The "effective dose 50" (ED 50) could be decreased by factor 34 in vivo in mouse ovulation test by reason of protection effect of polyglycine for the hormone against untimely proteolytical degradation.

Gliadins from wheat flour were extracted with 70% aqueous ethanol and hydrolyzed with alpha-chymotrypsin. Eight peptides, which seemed adequate as specific indicators for wheat ('Leitpeptide'), were isolated from the partial hydrolysate by RP-HPLC and analyzed for their amino acid sequences. Six of them were attributed to gliadin sequences already described in the literature, whereas two peptides represented novel sequence variations. Parallel investigations on the corresponding partial hydrolysates of prolamins from rye, barley, oats and maize showed that the isolated peptides were specific for wheat. A search in the protein data bank MIPS X (as of January 23 rd, 1990) did not produce any identical sequence. The 'Leitpeptide' allows the sensitive and specific recognition of wheat in complex and heated systems by RP-HPLC. They could be used also as the basis for immunochemical tests which would be convenient in routine analysis.