Pyridoxal phosphate. 5. 2-Formylethynylphosphonic acid and 2-formylethylphosphonic acid, potent inhibitors of pyridoxal phosphate binding and probes of enzyme topography.
The title compounds (17 and 21) were prepared in good yield by synthesis of the phosphonate diester acetals (14 and 19), deesterification with chloro- or bromotrimethylsilane, hydrolysis of the acetal group, and formation of the characterized barium salts. The 3-carbon aldehydrophosphonic acids (17 and 21) were potent inhibitors (Ki = 2 X 10(-6)) of pyridoxal phosphate (PPal) binding to apoaspartate aminotransferase (AAT) and are believed to span between and bind to the enzymic functional groups which bind the aldehyde and phosphate groups of PPal.
D001051:Apoenzymes / Q000378:metabolism*; D001059:Apoproteins / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D007700:Kinetics; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D001051:Apoenzymes; D001059:Apoproteins; D063065:Organophosphonates; D011732:Pyridoxal Phosphate; D001219:Aspartate Aminotransferases