Paralog-Selective Ligands for Bcl-2 Proteins

摘要

There is considerable interest in molecules that bind intra- or extracellular protein surfaces and inhibit protein-protein interactions.Molecules with these properties have potential as validation tools or therapeutic leads for the vast array of proteins encoded by the human genome and can probe the functional relevance of molecular circuits that control the inner workings of the cell.Accurate interpretation of such chemical biology experiments,however,demands an exceedingly high and often elusive level of specificity,as the phenotypic readout will reflect the weighted integral of all cellular binding events,whether they involve the desired target or not.This caveat is especially important when closely related protein family members or paralogs are coexpressed and nonredundant.