5324-47-0Relevant articles and documents
Discovery, Synthesis and Evaluation of a Ketol-Acid Reductoisomerase Inhibitor
Bayaraa, Tenuun,Kurz, Julia L.,Patel, Khushboo M.,Hussein, Waleed M.,Bilyj, Jessica K.,West, Nicholas P.,Schenk, Gerhard,McGeary, Ross P.,Guddat, Luke W.
, p. 8958 - 8968 (2020/07/04)
Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway, is a potential drug target for bacterial infections including Mycobacterium tuberculosis. Here, we have screened the Medicines for Malaria Venture Pathogen Box against purified M. tuberculosis (Mt) KARI and identified two compounds that have Ki values below 200 nm. In Mt cell susceptibility assays one of these compounds exhibited an IC50 value of 0.8 μm. Co-crystallization of this compound, 3-((methylsulfonyl)methyl)-2H-benzo[b][1,4]oxazin-2-one (MMV553002), in complex with Staphylococcus aureus KARI, which has 56 % identity with Mt KARI, NADPH and Mg2+ yielded a structure to 1.72 ? resolution. However, only a hydrolyzed product of the inhibitor (i.e. 3-(methylsulfonyl)-2-oxopropanic acid, missing the 2-aminophenol attachment) is observed in the active site. Surprisingly, Mt cell susceptibility assays showed that the 2-aminophenol product is largely responsible for the anti-TB activity of the parent compound. Thus, 3-(methylsulfonyl)-2-oxopropanic acid was identified as a potent KARI inhibitor that could be further explored as a potential biocidal agent and we have shown 2-aminophenol, as an anti-TB drug lead, especially given it has low toxicity against human cells. The study highlights that careful analysis of broad screening assays is required to correctly interpret cell-based activity data.
Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures
Klinker, Kristina,Sch?fer, Olga,Huesmann, David,Bauer, Tobias,Capel?a, Leon,Braun, Lydia,Stergiou, Natascha,Schinnerer, Meike,Dirisala, Anjaneyulu,Miyata, Kanjiro,Osada, Kensuke,Cabral, Horacio,Kataoka, Kazunori,Barz, Matthias
supporting information, p. 9608 - 9613 (2017/08/01)
Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple yet powerful approach to versatile peptide-based core–shell nanostructures.
Studies on Sulphochlorination of Paraffins. VIII. Studies on the Hydrolysis of Individual Alkane Sulphochlorides by Sodium Hydroxide
Hampel, M.,Just, G.,Krebes, W.,Pritzkow, W.
, p. 987 - 990 (2007/10/02)
The hydrolysis of individual C1-C5 alkane sulphochlorides by sodium hydroxide in dioxane/water (1:1) was kinetically studied at 25 deg C by means of stopped-flow technique, measuring the change of electric conductivity.The rate constants were influenced by steric hindrance, but in all cases were higher than the rate constant for alkaline hydrolysis of benzene sulphochloride, which cannot react according to the elimination-addition (sulphene) mechanism.The reaction enthalpy of the alkaline hydrolysis of four individual alkane sulphochlorides was determined by a simple calorimetric apparatus; the average value amounts to ΔRH = -239 kJ mol-1.
