The first mechanism-based inactivators for angiotensin-converting enzyme.

@article{Ghosh1992TheFM,
  title={The first mechanism-based inactivators for angiotensin-converting enzyme.},
  author={S. S. Ghosh and O E Said-Nejad and Juliatek Roestamadji and Shahriar Mobashery},
  journal={Journal of medicinal chemistry},
  year={1992},
  volume={35 22},
  pages={4175-9}
}
The first example of mechanism-based inactivation of angiotensin-converting enzyme (ACE) is described for N-[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (compound 1). It is proposed that an ACE-mediated deprotonation of 1 unmasks a ketenimine intermediate, which traps an active-site nucleophile, and hence irreversibly modifies the enzyme. In competition with the inactivation reaction, ACE also hydrolyzes 1 with a partition ratio of 8300 (i.e., kcat/kinact). Since the corresponding keto… CONTINUE READING