Selective probes into the mechanism of biotin action : the selection, syntheses, and spectral properties of s-methylated derivatives of thiobiotin and other biotin analogs

Biotin (1)) is a pivotal cofactor in numerous naturally occurring carbon dioxide transfer reactions. The detailed mechanisms of biotin dependent reactions at the molecular level are not well understood. In an effort to gain information concerning these mechanisms a series of S-methylated 2-thiobiotin based affinity labels were prepared. These substrates should yield information concerning the microenvironment of active sites in biotin dependent enzymes in general, and more specifically the biotin carboxylase (BC) and carboxyltransferase (CT) subunits of E. coll acetyl-CoA carboxylase. The rationale utilized in the selection of the desired probes is discussed. Furthermore, supportive model studies showing the feasability of synthesis as well as the likely utility of the selected probes as enzyme affinity labels are documented in this dissertation. [...]