Conformation of cyclo-(D-phenylalanyl-trans-4-fluoro-D-prolyl)

• Published in: International journal of peptide and protein research Vol. 36; no. 3; p. 285
• Main Authors: Ciarkowski, J, Gdaniec, M, Kołodziejczyk, A, Liberek, B, Borremans, F A, Anteunis, M J
• Format: Journal Article
• Language: English
• Published: Denmark 01.09.1990
• Subjects: Magnetic Resonance Spectroscopy; Models, Molecular; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Protein Conformation; X-Ray Diffraction
• ISSN: 0367-8377
• DOI: 10.1111/j.1399-3011.1990.tb00980.x

cyclo(D-Phenylalanyl-trans-4-fluoro-D-prolyl), c(D-Phe-D-FPro), was synthesized and its conformation determined both in solution and in the solid state by 1H NMR and X-ray analysis, respectively. In the crystals the 2.5-diketopiperazine (DKP) ring assumes the uncommon conformation, for cyclodipeptides containing Pro residue, of a flattened chair, which seemingly results from a compromise between, on the one hand, the DKP-aromatic intramolecular ring-ring attraction (folding), requiring the C alpha--C beta bond of the Phe to be axial, and, on the other hand, the intrinsic tendency of the Pro residue to have its C alpha--C beta bond equatorial. Unlike the solid state, the 1H NMR data in CDCl3 and C6D6 demonstrate that in both solutions the DKP ring assumes a boat-like shape, typical for the Pro-containing cyclodipeptides, with the equatorial C alpha--C beta bonds in both amino acid residues, which preclude ring-ring folding. A similar conformation was encountered in the closest analog of c(D-Phe-D-FPro), viz, in c(Phe-Pro), both in solution (21, 22, 26) and in the solid state (12). A subtle interplay of intramolecular interactions introduced into a cyclodipeptide by a Pro-type and a Phe-type residue is emphasized.