Suppression of problematic compound oligomerization by cosolubilization of nondetergent sulfobetaines

ChemMedChem
Yumiko MizukoshiIchio Shimada

Abstract

Numerous small organic compounds exist in equilibrium among monomers, soluble oligomers, and insoluble aggregates in aqueous solution. Compound aggregation is a major reason for false positives in drug screening, and even soluble oligomers can interfere with structural and biochemical analyses. However, an efficient way to manage the equilibrium of aggregation-prone compounds, especially those involved with soluble oligomers, has not been established. In this study, solution NMR spectroscopy was used as a suitable technique to detect compound oligomers in equilibrium, and it was demonstrated that cosolubilization of nondetergent sulfobetaines (NDSBs) can largely suppress compound oligomerization and aggregation by shifting the equilibrium toward the monomers. The rotational correlation time was obtained from the ratio of the selective and nonselective longitudinal NMR relaxation times, which directly and quantitatively reflected the apparent sizes of the compounds in the equilibrium. The rotational correlation time of the aggregation-prone compound SKF86002 (1 mM) was substantially reduced from 0.31 to 0.23 ns by cosolubilization of 100 mM NDSB195. NDSB cosolubilization allowed us to perform successful structural and biochemica...Continue Reading

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Citations

Apr 20, 2020·Journal of Biomolecular NMR·Hiroyuki HanzawaHideo Takahashi

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Methods Mentioned

BETA
NMR
chemical shift

Software Mentioned

WaterLOGSY
Topspin
INPHARMA

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