Small-molecule inhibitor: puromycin

Name

History: It seems that the first mention of puromycin as a peptidase inhibitor was that of McDonald et al. (1968).
Peptidases inhibited: Dipeptidyl-peptidase II and cytosol alanyl aminopeptidase.
Mechanism: Inhibition is reversible, but its mechanism is not entirely clear. The inhibition of dipeptidyl-peptidase II was competitive with substrate (Lys-Ala-2-naphthylamide), with K_i 1.9 x 10^-5 M. Smaller cations were found to inhibit, but proportionately more weakly (McDonald et al., 1968). Cytosol alanyl aminopeptidase (often termed puromycin-sensitive aminopeptidase) is inhibited with a K_i of 186 nM (Dando et al., 1997). By contrast, inhibition of aminopeptidase M is not significant, with K_i about 100 micromolar (Solhonne et al., 1987). Puromycin (10 micromolar) has been used to distinguish aminopeptidase M (still active) from cytosol alanyl aminopeptidase (inhibited) (Gillespie et al., 1992). Most other peptidases are unaffected by puromycin, but aminopeptidase PILS has been termed 'puromycin-insensitive aminopeptidase', presumably to distinguish it from cytosol alanyl aminopeptidase (Schomburg et al., 2000).

CID at PubChem: 4984
ChEBI: 580537
Structure
Chemical/biochemical name: 2-amino-N-[5-(6-dimethylaminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]-3-(4-methoxyphenyl)propanamide
Formula weight: 472