Small-molecule inhibitor: 1,10->phenanthroline

Name

Common name: 1,10-phenanthroline
Other names: o-phenanthroline; 1,10-phenanthroline-5,6-dione; OP; Phendione; PhN

History: An early example of the use of 1,10-phenanthroline (OP) for the inhibition of a peptidase (carboxypeptidase A) is the study of Felber et al. (1962).
Peptidases inhibited: Particularly the zinc metallopeptidases. (Unlike EDTA, OP has little affinity for calcium ions: Salvesen & Nagase, 2001.)
Mechanism: Usually the zinc ion is removed to yield an inactive apoenzyme. In some cases an inactive ternary complex may be formed. A detailed study of the mechanism of inhibition of astacin is that of Wolz & Zwilling (1989).

Solubility: OP has limited solubility in water, so a 100-fold stock solution in ethanol may be used.

Inhibitor class: This compound is of the metal chelator class. Metal chelators contain anionic or neutral oxygen, nitrogen or sulfur atoms spatially arranged so as to give bi-, tri- or tetradentate ligation to a metal atom. Chelators can inhibit metalloenzymes either by removal of the metal from the enzyme or by binding to it to form a ternary complex (Auld, 1995).
Comment: The apoenzymes of many of the matrix metallopeptidases in family M10 require calcium ions for stability, and the selectivity of OP for zinc allows it to be used in the presence of, say, 10 mM Ca²⁺, so that the apoenzyme may subsequently be reactivated (Salvesen & Nagase, 2001).
In work with OP, the non-chelating analogue, 1,7-phenanthroline, is sometimes used as a control for non-specific inhibition such as that of miltpain (C01.093: Kawabata & Ichishima, 1997).
Reviews: Auld (1988)