Binding site elucidation of a small molecule inhibitor of FtsZ

Binding site elucidation of a small molecule inhibitor of FtsZ

Nepomuceno, Gabriella M.; Anderson, David E.; Tadeus, Clarissa; Wang, Qian; Painter, Phillip P.; Chan, Katie M.; O’Brien, Terrence E.; Sarabia, Francisco J.; Tantillo, Dean J.; Ames, James B.; Lebrilla, Carlito; Shaw, Jared T.

Abstract:

Bacterial infections are becoming increasingly resistant to available antibiotics, often through a common mechanism of evolution to prevent the binding of drug molecules. While the development of new antibiotics for established targets is one approach to combat these infections, there is a rising need to consider alternate proteins or pathways. The bacterial cell division protein, FtsZ, therefore offers a new area for therapeutic research. Recently, several reported FtsZ inhibitors that led to a filamentatous phenotype were demonstrated to act through non-specific interactions. Zantrin Z3 (Z3) was the only molecule to maintain activity against B. subtilis (BsFtsZ) and E. coli (EcFtsZ). However, limited crystal data for BsFtsZ and EcFtsZ makes the development of more potent analogs difficult.

Bacterial infections are becoming increasingly resistant to available antibiotics, often through a common mechanism of evolution to prevent the binding of drug molecules. While the development of new antibiotics for established targets is one approach to combat these infections, there is a rising need to consider alternate proteins or pathways. The bacterial cell division protein, FtsZ, therefore offers a new area for therapeutic research. Recently, several reported FtsZ inhibitors that led to a filamentatous phenotype were demonstrated to act through non-specific interactions. Zantrin Z3 (Z3) was the only molecule to maintain activity against B. subtilis (BsFtsZ) and E. coli (EcFtsZ). However, limited crystal data for BsFtsZ and EcFtsZ makes the development of more potent analogs difficult.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013101518504

Referências bibliográficas

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Como citar:

Nepomuceno, Gabriella M.; Anderson, David E.; Tadeus, Clarissa; Wang, Qian; Painter, Phillip P.; Chan, Katie M.; O’Brien, Terrence E.; Sarabia, Francisco J.; Tantillo, Dean J.; Ames, James B.; Lebrilla, Carlito; Shaw, Jared T.; "Binding site elucidation of a small molecule inhibitor of FtsZ", p-132-132. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013101518504