Small-molecule inhibitor: pepstatin
Name
- Common name
- pepstatin
- Other names
- pepstatin A; S-PI
Inhibition
- History
- Pepstatin was discovered as an inhibitor of pepsin by Umezawa et al. (1970). An N-acetyl variant was described independently by Fukumura et al. (1971). Until 1970, no potent reversible inhibitors of aspartic peptidases had been known.
- Peptidases inhibited
- Pepstatin inhibits peptidases in families A1 and A2 (e.g. Fujinaga et al., 1995; Prashar et al., 2004). It also inhibits Alzheimer"s gamma-secretase, an activity of presenilin: Tian et al., 2002), which is an unrelated aspartic peptidase.
- Mechanism
- Pepstatin is a tight-binding, reversible inhibitor, acting as an analogue of the tetrahedral intermediate in catalysis. The minimal structural requirements for tight-binding inhibition of pepsin were explored by Rich & Bernatowicz (1982). A typical Ki value is that of 5 x 10-10 M obtained for human cathepsin D (Knight & Barrett, 1976).
Chemistry
![[pepstatin (A01.001 inhibitor) structure ]](/merops/smi/structures/pepstatin.gif)
General
- Comment
- Many structural variants of pepstatin are known, and the beta-amino acid termed statine that is contained in pepstatin has been used in the development of other inhibitors (Agarwal & Rich, 1986). Immobilized derivatives of pepstatin have proved to be effective ligands for affinity purification of aspartic peptidases (Suzuki et al., 1981; Rittenhouse et al., 1990).
- Reviews
- Szewczuk et al. (1992)
