Abstract
As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtke "fleximers", and Herdewijn's C5 substituted 2’-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti-coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review.
Keywords: Acyclic, antiviral, drug design, drug resistance, flexible, nucleoside.
Current Medicinal Chemistry
Title:Flexibility as a Strategy in Nucleoside Antiviral Drug Design
Volume: 22 Issue: 34
Author(s): H. L. Peters, T. C. Ku and K. L. Seley-Radtke
Affiliation:
Keywords: Acyclic, antiviral, drug design, drug resistance, flexible, nucleoside.
Abstract: As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtke "fleximers", and Herdewijn's C5 substituted 2’-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti-coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review.
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Cite this article as:
Peters L. H., Ku C. T. and Seley-Radtke L. K., Flexibility as a Strategy in Nucleoside Antiviral Drug Design, Current Medicinal Chemistry 2015; 22 (34) . https://dx.doi.org/10.2174/0929867322666150818103624
DOI https://dx.doi.org/10.2174/0929867322666150818103624 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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