SOLUTION AND SOLID-STATE STRUCTURE OF AN AIB-CONTAINING CYCLODECAPEPTIDE INHIBITING THE CHOLATE UPTAKE IN HEPATOCYTES

The conformational analysis of synthetic cyclodecapeptide c(Pro-Phr-Ph e-Aib-Leu)(2) related to the cyclolinopeptide A, in the solid state an d solution, has been carried out by I-ray diffraction and nmr spectros copy. The structure of the monoclinic form obtained om methanol [ a = 11.351 (5) Angstrom, b = 27.455 (2) Angstrom, c = 12.716(8) Angstrom, beta = 99.65(3)degrees; space group P2(1),; Z = 2] shows the prescnce of six intramolecular NH ... CO hydrogen bonds, with formation of four turns (three of type I and one of type IIl) and two C-16 ring structu res. All peptide units are trans. The solution structure, as found by nmr; indicates that, at room temperature, the peptide is conformationa lly homogeneous; the structure determined is perfectly symmetrical and topological similar to that found in the solid state. The cyclodecape ptide exhibits similar biological activity to cyclolinopeptide A. (C) 1997 John Wiley & Sons, Inc.