A joint research group head by Chang-Lin TIAN, High magnetic field laboratory, Chinese Academy of Sciences and Lei LIU, Tsinghua University, synthesized several bioactive disulfide-bond mimics of tachyplesin I, which is a 17-residue bicyclic peptide with high antimicrobial activity, using the diaminodiacid strategy. Subsequent NMR structural analysis revealed that disulfide-bond and its mimics played important roles in stabilizing the conformation of antimicrobial peptide.

Toxic peptides can effectively inhibit the growth of bacteria, fungi and eukaryotic cell, and a variety of toxic peptides were found out to effectively inhibit or enhance the selectivity or gating of ion channels. However, these peptides usually contain several disulfide-bonds, and it causes the difficulties in obtaining the right conformation without disulfide-bond mismatch using genetic engineering or chemical synthesis methods. To solve this problem, scientists replaced the disulfide-bond (Cys-S-S-Cys) with Cys-C-C-Cys or Cys-C-S-Cys using diaminodiacid-based solid-phase synthesis. This method not only leads to a quite considerable yields of peptides, but also avoids the mismatch of disulfide bond effectively. Researchers also assigned the chemical shift values of the 9 peptides using solution NMR and solved the 3-dimensional structures of 4 peptides. Analysis of the NMR data of peptides revealed that different disulfide bond mimics showed different abilities in stabilizing the conformation of peptides.

The research results entitled "Diaminodiacid-Based Solid-Phase Synthesis of Peptide Disulfide Bond Mimics" was accepted by Angewandte Chemie International Edition and published online at June 26th, 2013 (doi: 10.1002/ anie.201302197).

Relative link to this article: http://dx.doi.org/10.1002/anie.201302197.