BIOACTIVE PEPTIDES - X-RAY AND NMR CONFORMATIONAL STUDY OF [AIB(5,6)-D-ALA(8)]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) angstrom, b = 19.85 (3) angstrom, c = 9.90 (1) angstrom, space group P2(1)2(1)2(1), Z = 4], shows the presence of five intramolecular N-H...O=C hydrogen bonds, with formation of one C17 ring structure, one alpha-turn (C-13), one gamma-turn (C7), and two beta-turns (C10, one of type III and one of type I). The Pro1-Pro2 peptide unit is cis (omega = 9-degrees), 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.