Conformational analysis of cyclolinopeptide A, a cyclic nonapeptide: Nuclear overhauser effect and energy minimization studies

✍ Scribed by S. Raghothama; C. Ramakrishnan; D. Balasubramanian; P. Balaram

• Publisher: Wiley (John Wiley & Sons)
• Year: 1989
• Tongue: English
• Weight: 860 KB
• Volume: 28
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360280204

✦ Synopsis

The conformation of cyclolinopeptide A [ cyclo(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val)], a naturally occurring cyclic nonapeptide has been investigated in dimethylsulfoxide solution by 270 MHz 'H-nmr. A complete assignment of all C"H and NH resonances has been accomplished using two-dimensional correlated spectroscopy and nuclear Overhauser effects (NOES). Analysis of interresidue NO& and JHNCaH values pennit construction of a molecular model for the cyclic peptide backbone. The crude model derived from nmr has been used as a starting point for energy minimization, which yields a refined structure largely compatible with nmr observations. The major features of the conformation of cyclolinopeptide A are a Type VI /%turn centered at Pro(l)-Pro(P), with a cis peptide bond between these residues and a y-turn (C, structure) centered at 1146). Two intramolecular hydrogen bonds Val(9) CO-Phe(3)NH (4 -D 1) and Leu(5) CO-Ile(7)NH (3 -D 1) are observed in the low-energy conformation. The limited solvent accessibility observed for the Val(9) and Leu(5) NH groups in the nmr studies are rationalized in terms of steric shielding.