Cyclic B-Tetra- and Pentapeptides: Synthesis through On-Resin Cyclization and Confomrational Studies by X-Ray, NMR and CD Spectroscopy and Theoretical Calculations
2005 (English)In: Chem. Eur. J., Vol. 11, 6145-6158 p.Article in journal (Refereed) Published
The solution-phase synthesis of the simplest cyclic B-tetrapeptide, cyclo(B-Ala)4 (4), as well as the solidphase syntheses through side chain anchoring and on-resin cyclization of the cyclic B3-tetrapeptide cyclo-(B3hPhe-B3hLeu-B3hLys-B3hGln-) (14) and the first cyclic B3-pentapeptide cyclo- (B3hVal-B3hPhe-B3Leu- B3hLys-B3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(B-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-B3-tetrapetpride causes stabilizaton of one dominating conformer. The cyclic B3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(B-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectorscopic examinations of all cyclic B-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.
Place, publisher, year, edition, pages
2005. Vol. 11, 6145-6158 p.
conformation analysis, cyclization, NMR spectroscopy, peptides
IdentifiersURN: urn:nbn:se:uu:diva-74676DOI: doi:10.1002/chem.200500249OAI: oai:DiVA.org:uu-74676DiVA: diva2:102586