Bioactive Peptides: X-ray and NMR Conformational Study of [Aib5,6-D-Ala8]cyclolinopeptide A

The conformational analysis of [Aib5,6-D-Ala8]cyclolinopeptide A, in the solid state and solution, has been carried out by X-ray diffraction and NMR spectroscopy. The structure of the orthorhombic form, obtained from methanol-water mixture [a = 29.92 (3) Å, b = 19.85 (3) Å, c = 9.90 (1) Å, space group P212121 Z = 4], shows the presence of five intramolecular N-H…O=C hydrogen bonds, with formation of one C17 ring structure, one -turn (C13), one γ-turn (C7), and two β-turns (C10, one of type III and one of type I). The Pro1-Pro2 peptide unit is cis (ω = 9°), all others are trans. The conformational study in solution by NMR spectroscopy indicates that, even at room temperature, the peptide is conformationally homogeneous; the structure determined is almost identical to that observed in the solid state. The solution study reveals, also, that the constraints imposed by the two Aib and D-Ala residues are particularly strong, because the NMR conformational parameters are only slightly affected by wide temperature variations and salt addition. © 1992, American Chemical Society. All rights reserved.