MODELLING TRANSITION STATE ANALOGUES AND ENZYME-INHIBITOR COMPLEXES OF ZINC-CONTAINING CLASS II ALDOLASES AND METALLOPROTEASES

摘要

The zinc complex Tp*Zn-OH (1: Tp*=hydrotris-(3-cumyl,5-methyl-pyrazoryl)borate) which is a model of hydrolytic zinc enzymes was reacted with hydroxamic acids and hydroxyketones. Two hydroxamates Tp*Zn-Hya(2: Hya=acetohydroxamate, 3: Hya=2-hydroxamato-4-methylpentanoyl-alanyl-glycylamide) and two ketoalcoholates Tp*Zn-Kea (4: Kea=hydroxyacetonate, 5: Kea=cumoylacetonate) were obtained. Crystal structure determinations of 2, 3 and 5 have revealed distorted ZnN3O2 coordinations in each case. The immediate environment of the zinc ion in the hydroxamates closely resembles that in enzyme-(hydroxamate)inhibitor complexes of zinc-containing metalloproteases like collagenases and thermolysin or of class II aldolases like fuculose-1-phosphate aldolase. Like in the enzymes the hydroxamates and the ketoalcoholates can serve as transition state analogues of the enzyme-catalysed reactions. [References: 30]