Modulation of protein-protein interactions by synthetic receptors: design of molecules that disrupt serine protease-proteinaceous inhibitor interaction.
In the present article we describe the design and evaluation of a synthetic receptor that binds to the exterior surface of chymotrypsin and disrupts its interaction with proteinaceous inhibitors, such as soybean trypsin inhibitor, basic pancreatic trypsin inhibitor, ovomucoid turkey inhibitor, and Bowman-Birk inhibitor. Using enzyme kinetics, nondenaturing gel electrophoresis, and gel filtration chromatography we show that the receptor is particularly effective at blocking the chymotrypsin-soybean trypsin inhibitor complex and that the mechanism involves formation of an initial ternary complex followed by a time-dependent displacement of the proteinaceous inhibitor.
Park
Hyung Soon
HS
Department of Chemistry, Yale University, New Haven, CT, 06520, USA.
Lin
Qing
Q
Hamilton
Andrew D
AD
D002850:Chromatography, Gel; D002918:Chymotrypsin / Q000737:chemistry; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases / Q000737:chemistry*; D013997:Time Factors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry
D011506:Proteins; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D012697:Serine Endopeptidases; D002918:Chymotrypsin