Synthesis, conformation and biological activity of linear and cyclic Thr6-bradykinin analogues containing N-benzylglycine in place of phenylalanine

L. Biondi, F. Filira, M. Gobbo, B. Scolaro, R. Rocchi, R. Galeazzi, M. Orena, A. Zeegers, T. Piek

Research output: Contribution to journalArticlepeer-review

Abstract

Three linear Thr6-bradykinin analogues in which either one or both the two phenylalanine residues in the peptide sequence have been substituted by N-benzylglycine (BzlGly) and their head-to-tail cyclic analogues were synthesized and tested on an isolated rat duodenum preparation. The linear (BzlGly5,Thr6-BK, BzlGly8,Thr6-BK and BzlGly5.8,Thr6-BK) and the cyclic (cyclo BzlGly5,Thr6-BK, cyclo BzlGly8,Thr6-BK and cyclo BzlGly5.8, Thr6-BK) peptoid-like analogues were characterized by amino acid analysis, optical rotation, analytical HPLC and MALDI-TOF mass spectroscopy. The conformational features of both the linear and cyclic derivatives were investigated by FT-IR and CD measurements. Preliminary molecular mechanics calculations were also performed on some synthetic peptides. Pharmacological screening using the relaxation of the isolated rat duodenum preparation showed that incorporation of N-benzylglycine at positions 5 and/or 8 in the linear Thr6-BK causes a substantial decrease in potency. Comparable incorporation in cyclo Thr6-BK, at position 8, or 5 and 8, resulted in nearly inactive analogues. However, cyclo BzlGly5,Thr6-BK showed a potency which is of the same order of magnitude as for cyclo-BK and cyclo Thr6-BK.

Original languageEnglish
Pages (from-to)626-640
Number of pages15
JournalJournal of Peptide Science
Volume7
Issue number12
DOIs
Publication statusPublished - 2001

Keywords

  • Bradykinin
  • Kinins
  • N-alkylglycine
  • Peptoids
  • Synthesis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Fingerprint Dive into the research topics of 'Synthesis, conformation and biological activity of linear and cyclic Thr6-bradykinin analogues containing N-benzylglycine in place of phenylalanine'. Together they form a unique fingerprint.

Cite this