新《ACS传染病》杂志与其主编奥尔德里奇

诸平

         据美国化学会《化学与工程新闻》（C&EN）周刊网站2014年7月10日报道，美国化学会准备在2015年1月推出一种新杂志——《ACS传染病》（ACS Infectious Diseases）。美国明尼苏达大学（University of Minnesota）药物化学副教授考特尼·奥尔德里奇（Courtney C. Aldrich, E-mail: aldri015@umn.edu）博士将担任该杂志首任主编。

        《ACS传染病》是一种网络在线月刊杂志，主要专注于“传染病领域的基础科学进展和为临床科学奠定基础,”主题将包括“新发现的抗菌和抗病毒药物,药物靶点的鉴定与验证以及耐药性和发病机理的分子基础描述等。”

        美国化学会期刊出版集团的高级副总裁苏珊·金（Susan King）对此杂志的出版发行之事谈到，《ACS传染病》将会是第一个在多学科领域强调化学角色的一种杂志。担任此杂志主编的考特尼·奥尔德里奇博士，是美国明尼苏达大学药物设计中心（University of Minnesota’s Center for Drug Design）的副主任和副教授，他1994年在密苏里大学（Universityof Missouri ）获得化学硕士学位，2001年在美国加州大学洛杉矶分校（University ofCalifornia, Los Angeles）获得有机化学博士学位。2007～2013年担任明尼苏达大学药物设计中心的副主任。他的研究领域是具有新作用机理的抗菌药物以及小分子探针化学验证新生化目标物质的设计和合成。该杂志将从2014年9月份开始接受的相关研究领域的作者投稿。关于考特尼·奥尔德里奇博士的更多信息，请浏览：http://www.medicinal-chemistry.org/node/47.

Research Interest:
A primary objective of our research is to design new antibacterial agents basedon novel mechanisms of action. Currently, all clinically used antibiotics actby one of a limited number of mechanisms (e.g. inhibition of protein synthesis,DNA synthesis, cell-wall synthesis, and RNA transcription). We utilizeavailable data from experimental genetic approaches (random transposonmutagenesis, targeted genetic disruptions) as well as comparison to the humanproteome to identify candidate bacterial targets. In cases where the structureand enzymology of the bacterial enzyme is known, we rationally design substratemimics or transition-state inhibitors. However, for many potential targetsthere is inadequate structural information available to permit such astructure-based drug design approach. In these cases we develophigh-throughput-screening (HTS) assays that allow us to identify a leadcandidate molecule. Once a small molecule inhibitor is identified against thetargeted enzyme we then apply medicinal chemistry efforts to methodicallyoptimize the inhibitor scaffold. Structure- and/or ligand-based computationalapproaches are employed to rationalize activity data in order to refineinhibitor design. At an early stage we also test for antibacterial activityagainst the targeted organism(s) since whole-cell activity is a composite ofbinding affinity, membrane permeability, and stability. Additionally drugproperties of our inhibitors are evaluated using a variety of in vitro assaysto examine toxicity, absorption, and metabolism. Using this approach wedeveloped a new class of antibiotics that act by disruption of bacterial ironacquisition. We identified a previously unexplored target (an enzyme known asMbtA involved in biosynthesis of the mycobactins, which are small-moleculeiron-chelators produced by Mycobacterium tuberculosis) and described thedesign, synthesis, and biochemical evaluation of picomolar inhibitors effectiveagainst MbtA that also possess potent in vivo activity against Mycobacteriumtuberculosis. Since tuberculosis is the leading cause of bacterial infectiousdisease mortality this research is expected to have a positive impact on humanhealth and may additionally validate a new class of antibiotics thattarget siderophore biosynthesis.