Epoxide derivatives of pipecolic acid and proline are inhibitors of pipecolate oxidase.
The cis-4,5-epoxide derivative of L-pipecolic acid (2S,4S,5R-epoxypipecolic acid, cis-3) was synthesized and found to serve as an excellent substrate for L-pipecolate oxidase (L-PO) and also to cause time-dependent, irreversible inactivation of the enzyme. Data are presented showing this compound is a mechanism-based inhibitor of L-PO, whereas 2S,3R,4S-epoxyproline acts as a reversible inhibitor.
Ho
B
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College of Pharmacy, Oregon State University, Corvallis 97331-3507, USA.
Zabriskie
T M
TM
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D010875:Pipecolic Acids; D011392:Proline; D000587:Oxidoreductases Acting on CH-NH Group Donors; C032771:L-pipecolate dehydrogenase