hymecromone has been researched along with 4-(2-aminoethyl)benzenesulfonylfluoride* in 1 studies
1 other study(ies) available for hymecromone and 4-(2-aminoethyl)benzenesulfonylfluoride
Article | Year |
---|---|
Potent bivalent inhibition of human tryptase-beta by a synthetic inhibitor.
Human tryptase-beta (HTbeta) is a unique serine protease exhibiting a frame-like tetramer structure with four active sites directed toward a central pore. Potent inhibition of HTbeta has been attained using CRA-2059. This compound has two phenylguanidinium head groups connected via a linker capable of spanning between two active sites. The properties of the CRA-2059:HTbeta interaction were defined in this study. Tight-binding reversible inhibition was observed with an inhibition constant (Ki) of 620 pM, an association rate constant of 7x10(7) M(-1) s(-1) and a relatively slow dissociation rate constant of 0.04 s(-1). Bivalent inhibition was demonstrated by displacement of p-aminobenzamidine from the primary specificity pocket with a stoichiometry, [CRA-2059]0/[HTbeta]0, of 0.5. The potency of the bivalent interaction was illustrated by CRA-2059 inhibition of HTbeta, 24% or 53% inhibited by pre-incubation with an irreversible inhibitor. Two interactions were observed consistent with mono- and bi-valent binding; the Ki value for bivalent inhibition was at least 10(4)-fold lower than that for monovalent inhibition. Comparison of the affinities of CRA-2059 and phenylguanidine for HTbeta finds an approximate doubling of the free energy change upon bivalent binding. This doubling suggests that the linker portion minimally hinders the binding of CRA-2059 to HTbeta. The potency of CRA-2059 is thus attributable to effective bivalent binding. Topics: Benzamidines; Binding Sites; Binding, Competitive; Cross-Linking Reagents; Dioxoles; Fluorescent Dyes; Guanidines; Humans; Hymecromone; Kinetics; Osmolar Concentration; Protein Binding; Recombinant Proteins; Serine Endopeptidases; Serine Proteinase Inhibitors; Spectrometry, Fluorescence; Sulfones; Thermodynamics; Tryptases | 2003 |