A POTENT CYCLOLINOPEPTIDE-A ANALOG - SOLID-STATE AND SOLUTION CONFORMATION OF CYCLO [PRO-PHE-PHE-ALA-GLU(OTBU)](2)

The conformational analysis of cyclo[Pro-Phe-Phe-Ala-Glu(OtBu)](2), in the solid state and in solution, has been carried out by X-ray diffraction and NMR spectroscopy. The structure of the orthorhombic form obtained from dioxane-water-acetonitrile mixture [a = 9.994(1) Angstrom, b = 21.846(5) Angstrom, c = 37.357(9) Angstrom, space group P2(1)2(1)2(1); Z = 4] shows the presence of four intramolecular NH-CO hydrogen bonds, with formation of two beta turns (one of type I and one of type II) and two C-14 ring structures. All peptide units are trans. The solution structure, as determined by NMR, indicates that, at room temperature, the peptide is conformationally homogeneous; the structure determined is perfectly symmetrical and topologically similar to that found in the solid state. The cyclodecapeptide exhibits similar biological activity to cyclolinopeptide A.