Structure-Based Design and Development of Functionalized Mercaptoguanine Derivatives as Inhibitors of the Folate Biosynthesis Pathway Enzyme 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase from Staphylococcus aureus was written by Dennis, Matthew L.;Chhabra, Sandeep;Wang, Zhong-Chang;Debono, Aaron;Dolezal, Olan;Newman, Janet;Pitcher, Noel P.;Rahmani, Raphael;Cleary, Ben;Barlow, Nicholas;Hattarki, Meghan;Graham, Bim;Peat, Thomas S.;Baell, Jonathan B.;Swarbrick, James D.. And the article was included in Journal of Medicinal Chemistry in 2014.Electric Literature of C9H11BrO This article mentions the following:
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), an enzyme from the folate biosynthesis pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin and is a yet-to-be-drugged antimicrobial target. Building on our previous discovery that 8-mercaptoguanine (8MG) is an inhibitor of Staphylococcus aureus HPPK (SaHPPK), we have identified and characterized the binding of an S8-functionalized derivative (3). X-ray structures of both the SaHPPK/3/cofactor analog ternary and the SaHPPK/cofactor analog binary complexes have provided insight into cofactor recognition and key residues that move over 30 Å upon binding of 3, whereas NMR measurements reveal a partially plastic ternary complex active site. Synthesis and binding anal. of a set of analogs of 3 have identified an advanced new lead compound (11) displaying >20-fold higher affinity for SaHPPK than 8MG. A number of these exhibited low micromolar affinity for dihydropteroate synthase (DHPS), the adjacent, downstream enzyme to HPPK, and may thus represent promising new leads to bienzyme inhibitors. In the experiment, the researchers used many compounds, for example, 1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0Electric Literature of C9H11BrO).
1-(2-Bromoethyl)-4-methoxybenzene (cas: 14425-64-0) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Electric Literature of C9H11BrO
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary