A SELF-INCLUDED CYCLOMALTOHEPTAOSE DERIVATIVE STUDIED BY NMR-SPECTROSCOPY AND MOLECULAR MODELING

The 3D structure of 6-deoxy-6-L-tyrosinylamidocyclomaltoheptaose, a se lf-complexing beta-cyclodextrin derivative, was determined by NMR and molecular modelling. The aminoacyl side-chain is included in the cavit y and induces chemical-shift variations in the CD proton signals, allo wing their complete assignment. Dipolar interactions between protons o f the tyrosine ring and internal protons of the cyclodextrin were used to obtain distance constraints. Then 42 structures were calculated fr om 32 distance constraints - 21 shorter than 4 Angstrom involve the ho st-guest interactions - using a simulated annealing procedure. Startin g from one of the resulting structures, a 250-ps molecular dynamics si mulation was carried out in a waterbox without constraint. The simulat ion data are in agreement with NMR data such as nOe and ring-current e ffects. The cyclodextrin part takes an elliptical shape, which tightly fits the aromatic moiety. As a consequence, the respective motion of the host and the guest moieties have the same amplitude and time scale : the self-inclusion complex shows only little flexibility.