Courtney Aldrich, PhD

Associate Professor, Department of Medicinal Chemistry

Courtney Aldrich

Contact Info

aldri015@umn.edu

Office Phone 612-625-7956

Fax 612-626-3114

Office Address:
8-174 Weaver-Densford Hall

Mailing Address:
University of Minnesota
College of Pharmacy
Department of Medicinal Chemistry
8-101 Weaver-Densford Hall
308 Harvard St. SE
Minneapolis, MN 55455

Bachelor, University of Missouri, 1994

Summary

A primary objective of our research is to design new antibacterial agents based on novel mechanisms of action. Currently, all clinically used antibiotics act by one of a limited number of mechanisms (e.g. inhibition of protein synthesis, DNA synthesis, cell-wall synthesis, and RNA transcription). We utilize available data from experimental genetic approaches to identify candidate bacterial targets. In cases where the structure and enzymology of the bacterial enzyme is known, we rationally design substrate mimics or transition-state inhibitors. However, for many potential targets there is inadequate structural information available to permit such a structure-based drug design approach. In these cases we develop high-throughput-screening (HTS) assays that allow us to identify a lead candidate molecule. Once a small molecule inhibitor is identified against the targeted enzyme we then apply medicinal chemistry efforts to methodically optimize the inhibitor scaffold. Structure- and/or ligand-based computational approaches are employed to rationalize activity data in order to refine inhibitor design. At an early stage we also test for antibacterial activity against the targeted organism(s) since whole-cell activity is a composite of binding affinity, membrane permeability, and stability. Additionally drug properties of our inhibitors are evaluated using a variety of in vitro assays to examine toxicity, absorption, and metabolism.

Research

Research Summary/Interests

  • antibiotics
  • tuberculosis
  • synthesis
  • enzymology

Patents

  • Aldrich, C. C., “Antibacterial Agents,” (a) US Patent Appl. 0293666, filed Nov. 27, 2008; (b) EP Patent Appl. 1960518, filed Nov. 27, 2008; (c) PCT Intl. Patent Appl. PCT/US2006/046433, filed Jun 12, 2006, published June 14, 2007; (d) US Prov. Patent Appl. 60.742,729, filed Dec 6, 2005.
  • Aldrich, C. C.; Beck, B. J.; Gupte, A., “Antibiotic Triazole Derivatives of 5’-O-[N-(Salicyl)sulfamoyl] adenosine and Methods of Using Same” US Prov. Patent Appl. 61/112,418, filed Nov 7, 2008.
  • Aldrich, C. C.; Grimes, K.; Gupte, A. "Antibacterial FadD Inhibitor Compounds and Methods Treatment Using Same" US Prov. Patent Appl. 61/149,902, filed Feb 4, 2009.

Publications

  • Vasan, M.; Neres, J.; Williams, J.; Wilson, D. J.; Teitelbaum, A. M.; Remmel, R. P.; Aldrich, C. C. Inhibitors of the Salicylate Synthase (MbtI) from Mycobacterium tuberculosis Discovered by High-Throughput Screening. Chemmedchem 2010, 5, 2079–2087.
  • Wilson, D. J.; Aldrich, C. C. A Continuous Kinetic Assay for Adenylation Enzyme Activity and Inhibition. Anal. Biochem. 2010, 404, 56-63.
  • Shi, C.; Aldrich, C. C. Efficient Pd-Catalyzed Coupling of Tautomerizable Heterocycles with Terminal Alkynes via C-OH Bond Activation Using PyBroP. Org. Lett. 2010, 12, 2286-2289.
  • Sikora, A. L.; Wilson, D. J.; Aldrich, C. C.; Blanchard, J. S. Kinetic and Inhibition Studies of Dihydroxybenzoate-AMP Ligase (EntE) from Escherichia coli. Biochemistry 2010, 49, 3648-3657.
  • Grimes, K. D.; Gupte, A.; Aldrich, C. C. Copper(II)-Catalyzed Conversion of Aryl/Heteroaryl Boronic acids, -Boronates, and –Trifluoroboronates to the Corresponding Azides: Substrate Scope and Limitations. Synthesis 2010, 1441-1448.