Screening for Dimerization Inhibitors for Bacterial Acetyl CoA Carboxylase

Technical Report · Tue Nov 12 00:00:00 EST 2019

DOI:https://doi.org/10.2172/1573932· OSTI ID:1573932

Kent, Michael S. ^[1]; Sale, Kenneth L. ^[1]; Ricken, James Bryce ^[1]; Martinez, Daniella Victoria ^[1]; Juarros, Miranda ^[1]; Walrdop, Grover ^[2]

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1. Sandia National Laboratories (SNL), Albuquerque, NM, and Livermore, CA (United States)
2. Louisiana State University, Baton Rouge, LA (United States)

The goal of this project was to develop compounds that kill biothreat bacteria by inhibiting the activity of bacterial acetyl CoA carboxylase (ACC) by blocking dimerization of one component of that enzyme complex, biotin carboxylase (BC). The ultimate goal is to combine a BC dimerization inhibitor with an existing active site inhibitor for carboxytransferase, another component of ACC, to form a new dual inhibitor therapy for this essential enzyme to avoid onset of resistance. Developing medical countermeasures to defeat antibiotic resistance in biothreat agents is of interest for national security for protecting both warfighters and the public.

• Research Organization: Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States)
• Sponsoring Organization: USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
• DOE Contract Number: AC04-94AL85000; NA0003525
• OSTI ID: 1573932
• Report Number(s): SAND-2019-13612R; 681227
• Country of Publication: United States
• Language: English