ORGN 43 |
| Lawrence M. Sayre, Chunhua Qiao, and Heung-Bae Jeon. Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106 |
| b,g-Unsaturated primary amines like propargyl amine are known to inhibit bovine plasma amine oxidase (BPAO) via covalent modification of the enzyme active site, presumably reflecting alkylation by the reactive a,b-unsaturated aldehyde turnover product or the corresponding precursor product Schiff base. The g,d-unsaturated homolog, 1-amino-3-butyne (1), was found to be an unusually potent and irreversible inhibitor of BPAO, exhibiting a 30 min IC50 of 2.9 mM, despite the apparent unreactivity of the expected turnover product 3-butynal. However, the latter is known to tautomerize to the reactive alkylator, 2,3-butadienal (2). Interestingly, the substrate amine precursor to the latter aldehyde, 1-amino-2,3-butadiene (3) was found to be a more effective inhibitor of BPAO than 1, exhibiting a 5 min IC50 of 1.25 mM, though aldehyde 2 was found to be a much weaker inhibitor than either 1 or 3, suggesting that inactivation by the latter amines does not arise from turnover to 2 and alkylation of enzyme by accumulated 2. Whereas up to 5 mM mercaptoethanol did not protect the enzyme against inactivation by either 1 or 3, thiocholine bromide selectively protected against inactivation by 3. |
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Lipids, Biosynthesis, Enzyme Inhibitors, and Mimetics
8:00 AM-11:40 AM, Sunday, September 7, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry |