Exploring Flexible Purine Nucleobase Recognition by Biological Targets
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Date
2018-01-01
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Department
Chemistry & Biochemistry
Program
Chemistry
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Access limited to the UMBC community. Item may possibly be obtained via Interlibrary Loan thorugh a local library, pending author/copyright holder's permission.
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Abstract
FDA approved nucleos(t)ide analogue inhibitors are increasingly plagued by the rapid loss of efficacy due to the diseases' ability to develop resistance. Consequently, the development of novel drugs that work through alternative modes of action are needed. The Seley-Radtke laboratory is focused on synthesizing nucleos(t)ide analogues endowed with additional flexibility in the nucleobase that may aid in circumventing point mutations associated with resistance mechanisms. In addition to retaining the hydrogen bonding and aromatic character required for binding site recognition, flexible purine nucleosides, termed "fleximers,” possess several key advantages over normal nucleosides, notably the ability to adapt to a flexible enzyme binding site and possible mutations. To test their effectiveness, we have synthetically coupled these modified bases to clinically relevant 2'-fluorinated sugars. In addition, we are working to enzymatically couple fleximer bases to ribose or deoxyribose.