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Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamics
Author(s) -
Schievano Elisabetta,
Silvestri Laura,
Gobbo Marina,
Mammi Stefano,
Rocchi Raniero,
Peggion Evaristo
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.586
Subject(s) - conformational isomerism , chemistry , stereochemistry , cyclic peptide , kallidin , peptide bond , molecular dynamics , molecular model , crystallography , peptide , bradykinin , molecule , computational chemistry , biochemistry , receptor , organic chemistry , kinin
The conformational properties in DMSO of two head‐to‐tail cyclic analogues of kallidin ([Lys 0 ]‐bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr 6 ]‐KL ( YKL ), [Trp 6 ]‐KL ( WKL ), cyclo‐([Tyr 6 ]‐KL) ( YCKL ) and cyclo‐([Trp 6 ]‐KL) ( WCKL ). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo‐KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X‐Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X‐Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X‐Pro bond and always opposite configuration for the two consecutive X‐Pro bonds. The NOE‐restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.