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Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors.

ABSTRACT: Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order to improve its predicted binding affinity.The proposed binding modes of the resulting compounds mimic that of ATP, the native substrate, and provide insights into novel protein-ligand interactions that may be exploited in future drug-discovery projects.We are hopeful that these new predicted inhibitors will aid medicinal chemists in developing novel therapeutics to fight human African trypanosomiasis.

SUBMITTER: Durrant JD

PROVIDER: S-EPMC3196686 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors.

Durrant Jacob D JD McCammon J Andrew JA

BMC pharmacology 20110830

<h4>Background</h4>Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order to improve its predicted binding affinity.<h4>Results</h4>The proposed binding modes of the resulting compounds mimic that of ATP, the native substrate, and provide insight ...[more]

PMID: 21878090

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