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

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 beta-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) 3(10)-helix, the dipeptide methylamide adopts a type-II beta-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.

• Authors: G Valle, W M Kazmierski, M Crisma, G M Bonora, C Toniolo, V J Hruby
• Journal: International journal of peptide and protein research (Int J Pept Protein Res) 1992 Sep-Oct Vol. 40 Issue 3-4 Pg. 222-32 ISSN: 0367-8377 [Print] Denmark
• PMID: 1335996 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Isoquinolines
• Peptides
• Protons
• Solutions
• Tetrahydroisoquinolines
• 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• Phenylalanine

Topics

• Fourier Analysis
• Isoquinolines (chemistry)
• Magnetic Resonance Spectroscopy (methods)
• Models, Molecular
• Peptides (chemical synthesis)
• Phenylalanine (analogs & derivatives)
• Protein Conformation
• Protein Structure, Secondary
• Protons
• Solutions
• Spectrophotometry, Infrared
• Tetrahydroisoquinolines
• X-Ray Diffraction