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Full-Text Articles in Physical Sciences and Mathematics

In-Vial Detection Of Protein Denaturation Using Intrinsic Fluorescence Anisotropy, Krishnakumar Chullipalliyalil, Khaled Elkassas, Michael Mcauliffe, Sonja Vucen, Abina Crean Jan 2023

In-Vial Detection Of Protein Denaturation Using Intrinsic Fluorescence Anisotropy, Krishnakumar Chullipalliyalil, Khaled Elkassas, Michael Mcauliffe, Sonja Vucen, Abina Crean

Cappa Publications

The conventional quality control techniques for identifying the denaturation of biopharmaceuticals includes sodium dodecyl sulfate-polyacrylamide gel electrophoresis for identifying fragmentation, ion exchange chromatography and isoelectric focusing for identifying deamidation, reverse-phase high-performance liquid chromatography (HPLC) for identifying oxidation, and size-exclusion HPLC for identifying aggregation. These stability assessments require essential processes that are destructive to the product tested. All these techniques are lab based and require sample removal from a sealed storage vial, which can breach the sterility. In this work, we investigate the heat- and surfactant-induced denaturation of an in-vial-stored model protein, bovine serum albumin (BSA), by analyzing its intrinsic fluorescence …


An Improved Synthesis Of Adefovir And Related Analogues, Timothy P. O'Sullivan, Et Al Mar 2019

An Improved Synthesis Of Adefovir And Related Analogues, Timothy P. O'Sullivan, Et Al

Physical Sciences Publications

An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how …