Cyclic Tritrpticin Analogs with Distinct Biological Activities

Probiotics and Antimicrobial Proteins
Leonard T NguyenHans J Vogel

Abstract

Tritrpticin is a Trp-, Arg-, and Pro-rich cathelicidin peptide with promising antimicrobial activity. Cyclic analogs of tritrpticin were designed using two different approaches: circularization of the backbone by a head-to-tail peptide bond (TritrpCyc) or disulfide bridging between two Cys residues introduced at the termini of the peptide (TritrpDisu). Compared to the parent peptide, TritrpCyc has greatly improved therapeutic potential, showing stronger bactericidal activities and diminished hemolytic activity. Unexpectedly, the opposite effect was observed for TritrpDisu, which has lost its antimicrobial activity and is very hemolytic. In a membrane mimetic environment, NMR spectra show that TritrpDisu adopts an amphipathic turn-turn structure similar to linear tritrpticin. The structure of membrane-bound TritrpCyc has some similarity to that of TritrpDisu; however, the lipid interactions were not sufficient to restrain the structure of the former peptide in a single well-defined conformation. To help explain the distinct biological properties of the analogs, experiments investigating alternative antimicrobial targets were pursued: the membrane bilayer, lipopolysaccharides, and DNA. Although the hemolytic activity of TritrpDis...Continue Reading

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Citations

Mar 4, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mauricio AriasHans J Vogel
May 8, 2020·Biochimica Et Biophysica Acta. Biomembranes·Martijn RioolSebastian A J Zaat

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