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Cyclization of pyrrhocoricin retains structural elements crucial for the antimicrobial activity of the native peptide
Author(s) -
Rosengren K. Johan,
Göransson Ulf,
Otvos Laszlo,
Craik David J.
Publication year - 2004
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20159
Subject(s) - chemistry , antimicrobial , peptide , linker , derivative (finance) , stereochemistry , combinatorial chemistry , nuclear magnetic resonance spectroscopy , antimicrobial peptides , circular dichroism , cyclic peptide , two dimensional nuclear magnetic resonance spectroscopy , antibacterial activity , antibiotics , biological activity , in vitro , bacteria , biochemistry , organic chemistry , computer science , financial economics , economics , operating system , genetics , biology
Pyrrhocoricin is a naturally occurring antimicrobial peptide from the European fire bug Pyrrhocoris apterus. It has submicromolar activity against a range of Gram‐negative bacterial strains and has created recent interest as a lead for the development of novel antibiotic compounds. In this study, we have used NMR spectroscopy to determine the solution structures of pyrrhocoricin and a synthetic macrocyclic derivative that has improved in vivo pharmaceutical properties. Native pyrrhocoricin is largely disordered in solution, but there is evidence of a subpopulation with ordered turn regions over residues 2–5, 4–7, and 16–19. The macrocyclic derivative incorporates a nine amino acid linker joining the N‐ and C‐termini, which does not adversely affect the antimicrobial potency but leads to a broader spectrum of activity. The NMR data suggest that the turn conformations in the cyclic derivative are similar to those in the native form, thus implicating them in the biological function. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004