2017 June 26

Peptide Chemistry Laboratory

Although the nature can produce from the 20 coded amino acids almost uncountable number of proteins, the post-translational modifications of many proteins with a corresponding alteration in their biological and biochemical properties can form numerous entirely different compound from a single peptide chain. Synthetic peptides can be excellent models to study the conformational and functional changes following attachment of the side-chain moiety including sugar, phosphate, sulphate or lipidic groups. Up to now however, the synthetic capability to produce these "post-translationally modified " peptide fragments of larger proteins was very limited due to synthetic problems. With the recent availability of appropriately building blocks and modern synthetic techniques, the chemical synthesis of the upper modified peptides is no longer an obstacle to the proposed studies. Our task is the development of new methods for the chemical synthesis of various modified peptides containing post-translationally modified amino acid residues in different positions.

In addition to the above project we would like to work out new methods and building blocks for the preparation of conformationally constrained peptides. The reason of that is the following: Peptides are ubiquitous in living cells and assume myriad roles. Each role assumed by a bioactive peptide will typically correspond to a unique three dimensional structure. Although the short peptides are usually highly flexible molecules, the restriction of the conformational freedom can led to specific and highly active natural peptidomimetic molecules (e.g. several antibiotics, alkaloids, etc.). Based on this, the modulation of the conformation of short bioactive peptides can led to valuable lead compounds for the pharmaceutical industry.

The chemistry used to oxidize the free thiol (-SH) bonds to the corresponding disulfide (-S-S-) bond in a controlled fashion remains a significant challenge in spite of many advances in peptide chemistry. The primary reason of this the difficulties involved in the formation of multiple regioselective disulphide bonds. Recently a large number of multiple disulphide containing biologically active peptide are known, including peptide toxins, endothelins, insulins and miniproteins. Most of them have high biological importance. Not only their regioselective synthesis, but their structure proof is significant challenge.