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

Pre-resonance Raman spectroscopy has been applied to compare the vibra tional modes of the R and S chiral isomers of 1-deaza-7,8-dihydropteri dine when they are bound to tubulin. The main Raman bands are due to t he chromophore and are coupled with the pi-pi electronic transition o f C=C and C=N vibrational stretching. On binding to tubulin, the Raman spectra of both isomers are modified. However, the modifications indu ced are different for each isomer. The Raman bands due to C=C stretchi ng from the phenyl ring are more strongly modified for the bound R iso mer than for the S isomer. This leads us to suggest that R and S isome rs differ in terms of their orientation in front of the binding locus of tubulin. In fact, with respect to the orientation of the bulky meth yl group, the chromophore of the R isomer is more likely to be positio ned against the external surface of either tubulin or GTPase proteins, while that of the S isomer is likely to be positioned away from the s urface. The conformational changes induced in tubulin by R and S isome rs have also been studied by Fourier transform infrared spectroscopy a nd by the analysis of amide I and II absorption bands. Both enantiomer s induce similar minor changes to the tubulin secondary structure, cor responding to a decrease in the disordered alpha-helical content and a ccompanied by an increase in the undefined conformation content.