The complexation of peptides by aminocyclodextrins

Four beta -cyclodextrins (CDs) were prepared bearing either an (N,N-dimethy lamino)propylamino group (1), an (N-methyl)-piperazino group (2) or a benzy lamino group (3), or seven methylamino substituents (4). Association consta nts K in water with di- and tripeptides reach up to 200 M-1, and after prot ection at the N-terminus up to 680 M-1. Appreciable binding occurs only in the presence of lipophilic amino acid side-chains, with preference for this at the C-terminus. A moderate sequence and side-chain selectivity is obser ved with 1, 2 and 3, but less so with the highly charged 4 where ion pairin g dominates. Detailed NMR analyses with advanced techniques including T-ROE SY and GHSQC allow full assignment of most H-1 and C-13 signals, with extra ction of many substituent and complexation induced shifts changes (SIS and CIS values, respectively). The CIS values and NOE cross peaks from ROESY ex periments provide for insight into the binding modes of selected complexes, indicating, e.g., the simultaneous presence of complexes with a peptide ph enyl unit approaching from both the narrow and the wide side of the CD cavi ty. With 3 one observes self-inclusion of the pendant phenyl ring within th e cavity, and its replacement by analytes such as peptides, or by adamantan ecarboxylic acid. The inclusion modes are illustrated with force field simu lated structures and many NMR spectra, which are made available in electron ic supplements. Copyright (C) 2001 John Wiley & Sons, Ltd.