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.