Synthesis and properties of nicotinamide adenine dinucleotide analogs containing trichloroacetyl and trifluoroacetyl groups in position 3 of the pyridine ring.

Abstract

NAD analogs bearing trichloroacetyl and trifluoroacetyl groups in position 3 of the pyridine ring (I and II, resp.) were synthesized. The dinucleotide structures were confirmed by 1H NMR spectra and acid hydrolysis. These analogs did not interact either with Na sulfite or dithionite, seemingly because of the electron donating effect of the gem-diol substituent. I and II showed no substrate properties in the lactate dehydrogenase-catalyzed reactions; however, they effectively and competitively inhibited them with respect to NAD. I binding in the enzyme active site produced concomitant changes in the fluorescence spectra, analogous to these in model expts. brought about by lowering the solvent polarity. Ternary complex formation was not obsd. with lactate or oxamate. The possible interactions between the analogs and functional groups of the lactate dehydrogenase active center were discussed. [on SciFinder(R)]