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• W3003567179 abstract "ABSTRACT Small-molecule drugs are utilized in a wide variety of clinical applications, however, many of these drugs suffer from one or more suboptimal property that can hinder its delivery or cellular action in vivo, or even shelf an otherwise biologically tolerable drug. While high-throughput screening provides a method to discover drugs with altered chemical properties, directly engineering small-molecule bioconjugates provides an opportunity to specifically modulate drug properties rather than sifting through large drug libraries with seemingly ‘random’ drug properties. Herein, we propose that selectively “tethering” a drug molecule to an additional group with favorable properties will improve the drug conjugate’s overall properties, such as solubility. Specifically, we outlined the site-specific chemical conjugation of rapamycin (RAP) to an additional “high-affinity” group to increase the overall affinity the drug has for cyclodextrin-based polymers (pCD). By doing so, we found that RAP’s affinity for pCD and RAP’s window of delivery from pCD microparticles was tripled without sacrificing RAP’s cellular action. This synthesis method was applied to the concept of “affinity” for pCD, but other prosthetic groups can be used in a similar manner to modify other drug properties. This study displays potential for increasing drug delivery windows of small-molecule drugs in pCD systems for chronic drug therapies and introduces the idea of altering drug properties to tune polymer-drug interactions." @default.
• W3003567179 created "2020-02-07" @default.
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• W3003567179 date "2020-02-02" @default.
• W3003567179 modified "2023-09-26" @default.
• W3003567179 title "Engineering Selective Molecular Tethers to Enhance Suboptimal Drug Properties" @default.
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• W3003567179 doi "https://doi.org/10.1101/2020.02.01.929356" @default.
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