Structure Elucidation and Functional Studies of a Novel β-hairpin Antimicrobial Peptide from the Marine Polychaeta Capitella teleta
Autor: | Olesia V Reznikova, Ilia A. Bolosov, Tatiana V. Ovchinnikova, Pavel V. Panteleev, Andrey V Tsarev, Sergei V. Sychev, Victoria N Safronova, Zakhar O. Shenkarev |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
recombinant peptide antimicrobial peptide nuclear magnetic resonance (NMR) Antimicrobial peptides Pharmaceutical Science Peptide 01 natural sciences Capitella teleta law.invention 03 medical and health sciences law Drug Discovery BRICHOS domain Lipid bilayer lcsh:QH301-705.5 Pharmacology Toxicology and Pharmaceutics (miscellaneous) innate immunity chemistry.chemical_classification Innate immune system biology 010405 organic chemistry Chemistry β-hairpin structure biology.organism_classification Antimicrobial In vitro 0104 chemical sciences 030104 developmental biology lcsh:Biology (General) Biochemistry Recombinant DNA polychaeta |
Zdroj: | Marine Drugs Volume 18 Issue 12 Marine Drugs, Vol 18, Iss 620, p 620 (2020) |
ISSN: | 1660-3397 |
DOI: | 10.3390/md18120620 |
Popis: | Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play a key role in host defense. Among the most active and stable under physiological conditions AMPs are the peptides of animal origin that adopt a &beta hairpin conformation stabilized by disulfide bridges. In this study, a novel BRICHOS-domain related AMP from the marine polychaeta Capitella teleta, named capitellacin, was produced as the recombinant analogue and investigated. The mature capitellacin exhibits high homology with the known &beta hairpin AMP family&mdash tachyplesins and polyphemusins from the horseshoe crabs. The &beta hairpin structure of the recombinant capitellacin was proved by CD and NMR spectroscopy. In aqueous solution the peptide exists as monomeric right-handed twisted &beta hairpin and its structure does not reveal significant amphipathicity. Moreover, the peptide retains this conformation in membrane environment and incorporates into lipid bilayer. Capitellacin exhibits a strong antimicrobial activity in vitro against a wide panel of bacteria including extensively drug-resistant strains. In contrast to other known &beta hairpin AMPs, this peptide acts apparently via non-lytic mechanism at concentrations inhibiting bacterial growth. The molecular mechanism of the peptide antimicrobial action does not seem to be related to the inhibition of bacterial translation therefore other molecular targets may be assumed. The reduced cytotoxicity against human cells and high antibacterial cell selectivity as compared to tachyplesin-1 make it an attractive candidate compound for an anti-infective drug design. |
Databáze: | OpenAIRE |
Externí odkaz: |
Pro tento záznam nejsou dostupné žádné jednotky.