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Cyclic β‐Tetra‐ and Pentapeptides: Synthesis through On‐Resin Cyclization and Conformational Studies by X‐Ray, NMR and CD Spectroscopy and Theoretical Calculations
Author(s) -
Büttner Frank,
Norgren Anna S.,
Zhang Suode,
Prabpai Samran,
Kongsaeree Palangpon,
Arvidsson Per I.
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200500249
Subject(s) - tetrapeptide , conformational isomerism , pentapeptide repeat , cyclic peptide , side chain , chemistry , ring (chemistry) , stereochemistry , nuclear magnetic resonance spectroscopy , crystallography , peptide , molecule , organic chemistry , biochemistry , polymer
The solution‐phase synthesis of the simplest cyclic β‐tetrapeptide, cyclo(β‐Ala) 4 ( 4 ), as well as the solid‐phase syntheses through side chain anchoring and on‐resin cyclization of the cyclic β 3 ‐tetrapeptide cyclo(‐β 3 hPhe‐β 3 hLeu‐β 3 hLys‐β 3 hGln‐) ( 14 ) and the first cyclic β 3 ‐pentapeptide cyclo(‐β 3 hVal‐β 3 hPhe‐β 3 hLeu‐β 3 hLys‐β 3 hLys‐) ( 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(β‐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‐β 3 ‐tetrapeptide causes stabilization of one dominating conformer. The cyclic β 3 ‐pentapeptide on the other hand shows larger conformational freedom. The X‐ray structure of achiral cyclo(β‐Ala) 4 ( 4 ) displays a C i ‐symmetrical 16‐membered ring with adjacent CO and N‐H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic β‐peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.