Thermolysin inhibitors transition-state analogs

Figure 2. Phosphonamidate ( ), phosphinate (a), and phosphonate ( ) inhibitors of thermolysin as transition state analogs...

Bartlett PA, Marlowe CK. Phosphonamidates as transition-state analog inhibitors of thermolysin. Biochemistry 1983 22(20) 4618 624. 

Bartlett and Marlowe (153) designed a series of five phosphonamidate analogs of the peptide carbobenzoxy-Gly-Leu-X (X = NH2, Gly, Phe, Ala, Leu), where a -POz-NH- replaces the Gly-Leu peptide bond, and showed that these compounds were potent transition-state analog inhibitors of the zinc endopeptidase thermolysin. They also synthesized the corresponding phos-phonate analogs, where the -NH- (13A) is replaced by -O- (I3B). The... 

We have also looked at a series of tri- and tetrapeptide phosphonate inhibitors of carboxypeptidase A, with structural variation in the P2 and P3 residues.io Again, we see a good correlation between the Kj and Km/i cat values, supporting the view that the mechanisms of this enzyme and thermolysin are similar. This result is also consistent with the notion that a transition state analog motif that is good for one of these zinc peptidases should work the same way for the otho-. 

Bartlett, P.A. and Marlowe, C.K. (1983) Phosphonamidates as Transition State Analog Inhibitors of Thermolysin, Biochemistry, 22,4618-4624,... 

Tronrud DE, Monzingo AF, Matthews BW (1986) Crystallo-gnq)hic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin. Eur J Biochem 157 261-268... 

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