84365-04-8Relevant articles and documents
Synthesis, mechanism of action, and antiviral activity of a new series of covalent mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase
Guillerm,Guillerm,Vandenplas-Witkowki,Rogniaux,Carte,Leize,Van Dorsselaer,De Clercq,Lambert
, p. 2743 - 2752 (2001)
A direct method for the preparation of 5′-S-alkynyl-5′-thioadenosine and 5′-S-allenyl-5′thioadenosine has been developed. Treatment of a protected 5′-acetylthio-5′-deoxyadenosine with sodium methoxide and propargyl bromide followed by deprotection gave th
Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate
Bobi?eva, Olga,Bobrovs, Raitis,Ka?epe, Iveta,Patetko, Liene,Kalni??, Gints,?i?ovs, Mihails,Bula, Anna L.,Grī Nberga, Solveiga,Borodu??is, Mā Rti??,Ramata-Stunda, Anna,Rostoks, Nils,Jirgensons, Aigars,Tā Rs, Kaspars,Jaudzems, Kristaps
supporting information, p. 1102 - 1107 (2021/06/30)
Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase involved in cellular SAM/SAH ratio regulation was also determined, which indicated that the discovered compounds are nonselective inhibitors of the studied MTases with slight selectivity for Nsp16. No cytotoxic effects were observed; however, this is most likely a result of the poor cell permeability of all evaluated compounds.
Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine N-Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains1
Lu, Jian,Bart, Aaron G.,Wu, Qian,Criscione, Kevin R.,McLeish, Michael J.,Scott, Emily E.,Grunewald, Gary L.
, p. 13878 - 13898 (2020/12/02)
The enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) catalyzes the final step in the biosynthesis of epinephrine and is a potential drug target, primarily for the control of hypertension. Unfortunately, many potent PNMT inhibitors also po