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Folding propensity and biological activity of peptides: New insights from conformational properties of a novel peptide derived from Vitreoscilla haemoglobin
Author(s) -
Bozzi A.,
Coccia C.,
Di Giulio A.,
Rinaldi A. C.,
Amadei A.,
Mignogna G.,
Bonamore A.,
Fais A.,
Aschi M.
Publication year - 2007
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20792
Subject(s) - chemistry , peptide , antimicrobial peptides , membrane , folding (dsp implementation) , antimicrobial , biophysics , preprint , biochemistry , combinatorial chemistry , organic chemistry , biology , physics , electrical engineering , engineering , quantum mechanics
The synthetic peptide Vitr‐p‐13 (YPIVGQELLGAIK‐NH 2 ), derived from the bacterial dimeric Vitreoscilla haemoglobin (VHb) in the position 95–107, is characterized by a pre‐eminent “statistical coil” conformation in water as demonstrated by CD experiments and long time‐scale MD simulations. In particular, Vitr‐p‐13 does not spontaneously adopt an alpha‐helix folding in water, but it is rather preferentially found in beta‐hairpin‐like conformations. Long time‐scale MD simulations have also shown that Vitr‐p‐13 displays a “topological‐trigger” which initiates alpha‐helix folding within residues 7–10, exactly like seen in the temporins, a group of linear, membrane‐active antimicrobial peptides of similar length. At variance with temporins, in Vitr‐p‐13 such a process is energetically very demanding (+10 kJ/mol) in water at 300 K, and the peptide was found to be unable to bind model membranes in vitro and was devoid of antimicrobial activity. The present results, compared with previous studies on similar systems, strengthen the hypothesis of the requirement of a partial folding when still in aqueous environment to allow a peptide to interact with cell‐membranes and eventually exert membrane perturbation‐related antibiotic effects on target microbial cells. © 2007 Wiley Periodicals, Inc. Biopolymers 87: 85–92, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com