1984
DOI: 10.1002/med.2610040305
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The organic chemistry of mechanism‐based enzyme inhibition: A chemical approach to drug design

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1984
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Cited by 40 publications
(16 citation statements)
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References 98 publications
(8 reference statements)
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“…Denaturation of the inactivated enzyme did not lead to reoxidation of the flavin, indicating that attachment was to the flavin, as is the case with 1 -phenylcyclopropylamine (Silverman & Zieske, 1985). Consequently, these results suggest that PCBA is a mechanism-based (enzyme-activated) inactivator (Silverman & Hoffman, 1984;Walsh, 1984;Abeles, 1983;Rando, 1984) of MAO.…”
Section: Resultsmentioning
confidence: 77%
“…Denaturation of the inactivated enzyme did not lead to reoxidation of the flavin, indicating that attachment was to the flavin, as is the case with 1 -phenylcyclopropylamine (Silverman & Zieske, 1985). Consequently, these results suggest that PCBA is a mechanism-based (enzyme-activated) inactivator (Silverman & Hoffman, 1984;Walsh, 1984;Abeles, 1983;Rando, 1984) of MAO.…”
Section: Resultsmentioning
confidence: 77%
“…9 Their catalytic cycle involves removal of a proton, facilitating activation of many chemical entities. 1,3 We previously described dihydropyridone 1 as an MBI of BioA, 10 a PLP-dependent aminotransferase that conditional knockdown experiments identified as essential in Mycobacterium tuberculosis . 11 Given the presumed four-step mechanism of inactivation (Figure 1A), it was unclear how to further optimize 1 based on the obtained K I and k inact values.…”
mentioning
confidence: 99%
“…A mechanism-based inactivator is a chemically unreactive compound that is converted by an enzyme via its catalytic mechanism to a species that, without prior release from the active site, produces inactivation of that enzyme (Silverman & Hoffman, 1984;Walsh, 1984;Abeles & Maycock, 1976;Rando, 1974). The mechanism proposed for the inactivation of M A 0 by N-CBA was described in the preceding paper in this issue .…”
mentioning
confidence: 99%