Synthetic modifications of the antibiotic peptide gramicidin S : conformational and biological aspects

Abstract

The research described in this thesis focuses on synthetic modifications of the antibiotic peptide gramicidin S (GS). The aim of the research is the development of non__toxic analogs of GS using conformational and amphipathic changes induced by sugar amino acids (SAAs) and/or non__proteinogenic amino acids. The physical properties of the synthetic derivatives were studied using NMR, Molecular Modeling, Circular Dichroism, LC/MS, and X-ray techniques. Evaluation of the biological activity (antimicrobial activity and toxicity) of the peptides revealed that various synthetic derivatives appeared to be less toxic than GS. By the frequent use and misuse of antibiotics the amount of untreatable bacterial infections has increased. This research has contributed to the development of antibiotics for which resistance by bacteria should not easily occur.