Constrained phenylalanine analogues: Preferred conformation of the 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic) residue

G. VALLE, W. M. KAZMIERSKI, M. CRISMA, G. M. BONORA, C. TONIOLO, V. J. HRUBY

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Three Tic‐containing (Tic = 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid) model peptides were synthesized to assess the tendency of this constrained Phe analogue to fold into a β‐bend and a helical structure, and to adopt a preferred side‐chain disposition. The results of the solution conformational analysis, performed by using Fourier transform infrared absorption and 1H nuclear magnetic resonance, indicate that in chloroform the ‐Aib‐D‐Tic‐Aib‐, ‐(Aib)2‐D‐Tic‐(Aib)2‐, and ‐l‐Pro‐D‐Tic‐ sequences fold into intramolecularly H‐bonded forms to a great extent. An X‐ray diffraction analysis on p‐BrBz‐(Aib)2‐dl‐Tic‐(Aib)2‐OMe monohydrate and p‐BrBz‐l‐Pro‐D‐Tic‐NHMe allows us to conclude that, while the pentapeptide methylester forms an incipient (distorted) 310‐helix, the dipeptide methylamide adopts a type‐II β‐bend conformation. In both cases, the d‐Tic side‐chain conformation is d, gauche(‐). The implications for the use of the Tic residue in designing conformationally restricted analogues of bioactive peptides are briefly discussed.

Original languageEnglish (US)
Pages (from-to)222-232
Number of pages11
JournalInternational journal of peptide and protein research
Volume40
Issue number3-4
DOIs
StatePublished - Sep 1992

Keywords

  • 3‐helix
  • Tic peptides
  • X‐ray diffraction
  • conformational analysis
  • crystal‐state conformation
  • infrared absorption
  • nuclear magnetic resonance
  • peptide conformation
  • β‐bends

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Constrained phenylalanine analogues: Preferred conformation of the 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic) residue'. Together they form a unique fingerprint.

Cite this