Poster abstracts
Poster number 150 submitted by Andrew Yaldo
Experimental determination of pKa values of canonical and analogue nucleosides
Andrew A. Yaldo (Chemistry, Wayne State University ), Sun Jeong Im (Chemistry, Wayne State University ), Christine S. Chow (Chemistry, Wayne State University )
Abstract:
Nucleosides play critical roles in biological systems. Modified nucleoside analogues such as fleximers (synthetic variants of purine bases in which the bicyclic ring is split into two linked heterocycles) have shown potential as novel antiviral and cancer drugs. A key characteristic that plays a role in a molecule’s binding mode with a biological target is the pKa value. The pKa value is a measure of protonated or deprotonated states at specific locations on the molecule at a given pH value. The pKa values of nucleoside analogues such as fleximers have not been well studied. Depending on the protonation state, the compounds could have very different properties and participate in different interactions with a target molecule. In this study, the pKa values of nucleosides were determined experimentally using two methods: 1) carbon-13 NMR and chemical shift changes at varying pH conditions, and 2) UV-visible spectroscopy by measuring the absorbance values at various pH conditions. The pros and cons of both methods will be discussed alongside the experimental results. The ability to determine pKa values of analogue nucleosides will be beneficial for the development of novel drugs.
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Keywords: Fleximer, pKa