68887-68-3Relevant academic research and scientific papers
Dual-Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase
Ma, Nana,Chen, Zhifeng,Chen, Jie,Chen, Jingfei,Wang, Cong,Zhou, Haifeng,Yao, Lishan,Shoji, Osami,Watanabe, Yoshihito,Cong, Zhiqi
, p. 7628 - 7633 (2018/04/02)
We report a unique strategy for the development of a H2O2-dependent cytochrome P450BM3 system, which catalyzes the monooxygenation of non-native substrates with the assistance of dual-functional small molecules (DFSMs), such as N-(ω-imidazolyl fatty acyl)-l-amino acids. The acyl amino acid group of DFSM is responsible for bounding to enzyme as an anchoring group, while the imidazolyl group plays the role of general acid–base catalyst in the activation of H2O2. This system affords the best peroxygenase activity for the epoxidation of styrene, sulfoxidation of thioanisole, and hydroxylation of ethylbenzene among those P450–H2O2 system previously reported. This work provides the first example of the activation of the normally H2O2-inert P450s through the introduction of an exogenous small molecule. This approach improves the potential use of P450s in organic synthesis as it avoids the expensive consumption of the reduced nicotinamide cofactor NAD(P)H and its dependent electron transport system. This introduces a promising approach for exploiting enzyme activity and function based on direct chemical intervention in the catalytic process.
Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites
Olaleye, Tayo O.,Brannigan, James A.,Roberts, Shirley M.,Leatherbarrow, Robin J.,Wilkinson, Anthony J.,Tate, Edward W.
supporting information, p. 8132 - 8137 (2015/01/08)
N-Myristoyltransferase (NMT) has been shown to be essential in Leishmania and subsequently validated as a drug target in Plasmodium. Herein, we discuss the use of antifungal NMT inhibitors as a basis for inhibitor development resulting in the first sub-micromolar peptidomimetic inhibitors of Plasmodium and Leishmania NMTs. High-resolution structures of these inhibitors with Plasmodium and Leishmania NMTs permit a comparative analysis of binding modes, and provide the first crystal structure evidence for a ternary NMT-Coenzyme A/myristoylated peptide product complex. This journal is
Inhibiton of thromboxane synthetase with 1-substituted imidazole compounds
-
, (2008/06/13)
The imidazole compounds of the general formula (I): STR1 wherein Y is a carboxyl group, a hydroxymethyl group, an N-di or -mono alkyl substituted or unsubstituted carbamoyl group, a cyano group, or an N-di or -mono alkyl substituted or unsubstituted aminomethyl group, and n is an integer of 3 to 20; and pharmaceutically acceptable salts thereof. These compounds have a strong inhibitory effect on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for inflammation, hypertension, thrombus, cerebral apoplexy and asthma.
Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives
Iizuka,Akahane,Momose,Nakazawa,Tanouchi,Kawamura,Ohyama,Kajiwara,Iguchi,Okada,Taniguchi,Miyamoto,Hayashi
, p. 1139 - 1148 (2007/10/02)
The structure-activity relationships of imidazole derivatives as inhibitors of thromboxane (TX) synthetase were investigated. Introduction of various substituents (e.g., one or two methyl groups, a halogen atom, a methylidene group, unsaturated bonds, or a phenylene group) into the α position or other positions in the carboxy-bearing side chain of 1-(7-carboxyheptyl)imidazole was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum for the inhibitory potency on TX synthetase in the region of 8.5-9.0 A. Among the tested imidazole derivatives, 1-(7-carboxy-7-methyl-2-octynyl)imidazole, 4-[3-(1-imidazolyl)-propyl]benzoic acid, and (E)-4-(1-imidazolylmethyl)cinnamic acid and its α-methyl analogue showed the highest potency with an IC50 in the range of 10-8 to 10-9 M. Inhibition by these derivatives was highly selective for the TX synthetase, since other enzymes such as fatty acid cyclo-oxygenase and prostacyclin synthetase were not affected.
