Presented by: Brian Shoichet, Ph.D., University of California San Francisco
Presented Live: November 4, 2015 at the 24th International Light Scattering Colloquium, Santa Barbara, CA
At micromolar and sub-micromolar concentrations, many drug-like organic molecules aggregate into colloids in aqueous media. These colloidal aggregates sequester protein targets without specificity, inhibiting or occasionally even activating them—they are the single greatest source of artifact in early drug discovery. The colloidal species are about 200 nm in radius, and a major way to detect and characterize them is by dynamic light scattering. I will summarize the range of molecules that can aggregate, the range of assays in which they do so, including membrane-bound receptor and cell-culture assays, and the mechanism by which these colloidal aggregates act to sequester protein. Recent research on their effects on drug distribution in vivo will be considered, as will efforts to formulate them to actually optimize for drug and protein delivery.
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