Structure–activity relationships for the cardiotropic action of the Led‐NPF‐I peptide in the beetles Tenebrio molitor and Zophobas atratus
Author(s) -
Marciniak Paweł,
Grodecki Sebastian,
Konopińska Danuta,
Rosiński Grzegorz
Publication year - 2008
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.933
Subject(s) - peptide , proline , amino acid , chemistry , arginine , biological activity , histidine , biochemistry , valine , residue (chemistry) , peptide sequence , stereochemistry , in vitro , gene
Abstract We have examined the effects of the Led‐NPF‐I peptide (Ala‐Arg‐Gly‐Pro‐Gln‐Leu‐Arg‐Leu‐Arg‐Phe‐amide) and a series of ten analogues on the heart contractile activity of Tenebrio molitor and Zophobas atratus, and the structure–activity relationships for cardioactive action of Led‐NPF‐I were established. A video microscopy technique and computer‐based method of data acquisition and analysis were used to study the action of the peptides on continuously perfused heart preparations. Cardiac activity was progressively inhibited by Led‐NPF‐I when the peptide concentrations were increased from 10 −9 to 10 −5 M . Substitution of the L ‐proline residue at position 4 of the native peptide with hydroxyproline, valine or D ‐proline caused a loss of cardioinhibitory activity. Also, replacement of arginine residues at all three positions 2, 7 and 9 with another basic amino acid histidine, reduces cardioinhibitory action of Led‐NPF‐I. Some modifications of the C ‐terminal residues, as the Phe(4‐NO 2 )‐, Phe(4‐NH 2 )‐ and Phe(4‐NMe 2 )‐analogues, resulted in agonistic peptides with biological activity similar to that of the native peptide. However, three other C ‐terminal analogues tested [Tyr 10 ]‐, [D‐Phe 10 ]‐Led‐NPF‐I, and Ala‐Arg‐Gly‐Pro‐Gln‐Leu‐Arg‐Leu‐Arg‐Phe‐OH were inactive in the heart bioassay, which suggests that this end of the amino acid chain may play an important role in bioactivity and interaction of the native peptide with its receptor on the myocardium. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.