Structural Basis for the Selective Binding of Inhibitors to 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus and Escherichia coli was written by Dennis, Matthew L.;Pitcher, Noel P.;Lee, Michael D.;DeBono, Aaron J.;Wang, Zhong-Chang;Harjani, Jitendra R.;Rahmani, Raphael;Cleary, Ben;Peat, Thomas S.;Baell, Jonathan B.;Swarbrick, James D.. And the article was included in Journal of Medicinal Chemistry in 2016.Formula: C8H7BrO2 This article mentions the following:
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a member of the folate biosynthesis pathway found in prokaryotes and lower eukaryotes that catalyzes the pyrophosphoryl transfer from the ATP cofactor to a 6-hydroxymethyl-7,8-dihydropterin substrate. We report the chem. synthesis of a series of S-functionalized 8-mercaptoguanine (8MG) analogs as substrate site inhibitors of HPPK and quantify binding against the E. coli and S. aureus enzymes (EcHPPK and SaHPPK). The results demonstrate that analogs incorporating acetophenone-based substituents have comparable affinities for both enzymes. Preferential binding of benzyl-substituted 8MG derivatives to SaHPPK was reconciled when a cryptic pocket unique to SaHPPK was revealed by X-ray crystallog. Differential chem. shift perturbation anal. confirmed this to be a common mode of binding for this series to SaHPPK. One compound (41) displayed binding affinities of 120 nM and 1.76 μM for SaHPPK and EcHPPK, resp., and represents a lead for the development of more potent and selective inhibitors of SaHPPK. In the experiment, the researchers used many compounds, for example, 3-(Bromomethyl)benzoic acid (cas: 6515-58-8Formula: C8H7BrO2).
3-(Bromomethyl)benzoic acid (cas: 6515-58-8) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Formula: C8H7BrO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary