MOLECULAR INTERACTION OF TUBULIN WITH 1-DEAZA-7,8-DIHYDROPTERIDINES - A COMPARATIVE-STUDY OF ENANTIOMERS NSC-613862(S) AND NSC-613863(R) BY RAMAN AND FOURIER-TRANSFORM INFRARED-SPECTROSCOPY

Pre-resonance Raman spectroscopy has been applied to compare the vibrational modes of the R and S chiral isomers of 1-deaza-7,8-dihydropteridine when they are bound to tubulin. The main Raman bands are due to the chromophore and are coupled with the pi-pi* electronic transition of C=C and C=N vibrational stretching. On binding to tubulin, the Raman spectra of both isomers are modified. However, the modifications induced are different for each isomer. The Raman bands due to C=C stretching from the phenyl ring are more strongly modified for the bound R isomer than for the S isomer. This leads us to suggest that R and S isomers differ in terms of their orientation in front of the binding locus of tubulin. In fact, with respect to the orientation of the bulky methyl group, the chromophore of the R isomer is more likely to be positioned against the external surface of either tubulin or GTPase proteins, while that of the S isomer is likely to be positioned away from the surface. The conformational changes induced in tubulin by R and S isomers have also been studied by Fourier transform infrared spectroscopy and by the analysis of amide I and II absorption bands. Both enantiomers induce similar minor changes to the tubulin secondary structure, corresponding to a decrease in the disordered alpha-helical content and accompanied by an increase in the undefined conformation content.