PRELIMINARY-STUDY OF SUBSTRATE-BINDING TO THYMIDINE KINASE BY TRANSFERRED NOE

A series of substrates with different values of dissociation constants K-d characteristic of their interaction with thymidine kinase (TK) ha s been studied (thymidine, acyclovir and tricycle). In thymidine-TK so lutions ho transferred NOEs were observed which was attributed to the fact that the dissociation constant K-d is too low (similar to 8 mu M) . In both acyclovir and tricycle, however, K-d proved sufficiently hig h (similar to 400 mu M) to allow for the observation of negative (tran sferred) NOEs. Series of NOESY spectra were recorded for tricycle (pos itive NOEs) and for the tricycle-TK complex (negative NOEs). The NOE p attern remains the same in both cases which indicates that the structu re of the ligand does not change significantly upon binding to TK. The analysis of correlation patterns proves that the orientation of the a liphatic chain of tricycle with respect to the aromatic rings is chara cteristic of the syn conformation.