Development of foldamer building block containing antimicrobial peptides
The biggest advance of antimicrobial peptides and protein fragments is the limited appearance of bacterial resistance. Because of their enzymatic lability, nowadays higher ordered structures or non-natural foldamer-based compounds came into prominence. However, the amino acid replacement with artificial building blocks only on specific positions appears moderately in the toolbox of medicinal chemists.
We aim to investigate and develop self-organizing oligopeptide systems that interact with biological membranes, possess high antimicrobial activity and enzymatic stability. Within the project we aim to carry out an iterative sequence development based on the synergistic cooperation of two key areas; (i) in vitro efficacy testing on bacteria and host cell cultures and (ii) state-of-the-art continuous flow peptide synthesis.
The first key area is the research of Kata Horváti, which is on the synthesis of peptide-based molecules to prevent and treat tuberculosis and other bacterial infections. Within her research new peptide-conjugates were developed that effectively inhibited intracellular, mainly multiresistant microorganisms. The second key area is the research of István Mándity, which is based on the development of novel synthetic techniques. Among them the application of continuous-flow techniques is wide spreading. Foldamers are artificial self-organizing systems made from non-natural amino acids. These molecules possess properties similar to those of natural proteins. By the combination of these two fields, a state-of-the-art peptide synthesis reactor was developed, which allows the cost-efficient incorporation of β3-amino acid building blocks into antimicrobial peptide sequences.
Kata Horváti, István Mándity