The complexation of peptides by aminocyclodextrins

Abstract

Four β‐cyclodextrins (CDs) were prepared bearing either an (N,N‐dimethylamino)propylamino group (1), an (N‐methyl)‐piperazino group (2) or a benzylamino group (3), or seven methylamino susbtituents (4). Association constants K in water with di‐ and tripeptides reach up to 200 M −1, and after protection 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 observed with 1, 2 and 3, but less so with the highly charged 4 where ion pairing dominates. Detailed NMR analyses with advanced techniques including T‐ROESY and GHSQC allow full assigment of most 1H and 13C signals, with extraction of many substituent and complexation induced shifts changes (SIS and CIS values, respectively). The CIS values and NOE cross peaks from ROESY experiments provide for insight into the binding modes of selected complexes, indicating, e.g., the simultaneous presence of complexes with a peptide phenyl unit approaching from both the narrow and the wide side of the CD cavity. With 3 one observes self‐inclusion of the pendant phenyl ring within the cavity, and its replacement by analytes such as peptides, or by adamantanecarboxylic acid. The inclusion modes are illustrated with force field simulated structures and many NMR spectra, which are made available in electronic supplements. Copyright © 2001 John Wiley & Sons, Ltd. Additional material for this paper is available from the epoc website at http://www.wiley.com/epoc: (NMR shift tables; 3D coordinates for molecular structures; 1D‐ and 2D‐NMR spectra)

Binding Mechanisms in Supramolecular Complexes

“…[622] A domination of enthalpic driving forces is characteristic of hydrophobic interactions; for example, in the complexation of protected dipeptides with native g-CD these can reach À68 kJ mol À1 , generally with opposing entropy penalties of the same order of magnitude. [626] The association constants of nucleotides with aminocyclodextrins can exceed K = 10 6 m À1 , with complexes stabilized largely by salt bridges with heptaamino-b-CD, for example. [625] Relatively strong complexes of native di-and tripeptides with monoamino-b-CDs are observed only in the presence of lipophilic amino acid residues, which, according to NMR analysis, dip into the cavity.…”

“…Selectivity is largely lost with the use of heptaamino-b-CD because of the dominance of salt bridges. [626] The association constants of nucleotides with aminocyclodextrins can exceed K = 10 6 m À1 , with complexes stabilized largely by salt bridges with heptaamino-b-CD, for example. If the association constants are reduced, as with monoamino-b-CD, then a preference of roughly an order of magnitude is found for the larger purine derivatives AMP or GMP relative to UMP or CMP, a result consistent with stronger hydrophobic contributions.…”

Water-soluble, cyclodextrin-functionalized semiconductor nanocrystals: Preparation and pH-dependent aggregation and emission properties

“…Hepta-(per)-amino b-cyclodextrin has been prepared as described in detail elsewhere [30,31]. The ammonium salt of this compound is dissolved in water, and the pH of the aqueous solution is adjusted to 12 by the addition of tetramethyl ammonium hydroxide ((CH 3 ) 4 NOH).…”

Bindungsmechanismen in supramolekularen Komplexen

“…Die Selektivität geht bei Verwendung von Heptaamino-b-CD durch die dann dominierenden Salzbrücken weitgehend verloren. [626] Assoziationskonstanten von Nucleotiden mit Aminocyclodextrinen reichen bis über K = 10 6 m À1 bei überwiegend durch Salzbrücken stabilisierten Komplexen mit z. B. Heptaaminob-CD.…”