title: Synthesis of leupeptins and inhibition of proteinases. I. Inhibition of acrosin and trypsin.
abstract: A series of leupeptin analogs R-L-leucyl-L-leucyl-L-argininal with variable N-terminal substituents has been synthesized using N alpha-tert-butyl-oxycarbonyl-NG-benzyloxycarbonyl-L-arginine-delta-lactam as the starting material. The modified leupeptins proved to be strong competitive inhibitors of the endoprotease acrosin from mammalian spermatozoa. Inhibition constants were found in the range of 4.7 X 10(-7)M (R = H) to 9.7 X 10(-9)M (R = tert-butyloxycarbonyl). N alpha-tert-butyloxycarbonyl leupeptin represents the strongest acrosin inhibitor synthesized so far. Two of the leupeptin derivatives (R = trifluoroacetyl, R = tert-butyloxycarbonyl) were more effective than the natural leupeptins from microbial sources (Ki = 5.9 X 10(-8)M). The potential use of synthetic leupeptins as antienzymatic contraceptives is discussed.
mesh_terms: D000176:Acrosin / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D007202:Indicators and Reagents; D007700:Kinetics; D007976:Leupeptins / Q000138:chemical synthesis*; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis*; D011480:Protease Inhibitors; D013094:Spermatozoa / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine; D014361:Trypsin Inhibitors / Q000138:chemical synthesis*
chemical_list: D007202:Indicators and Reagents; D007976:Leupeptins; D009842:Oligopeptides; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D000176:Acrosin