residuespecific

Residue-specific refers to processes, reagents, or enzymes that selectively react with particular amino acid residues or functional groups within proteins or peptides. The term is used to distinguish these targeted interactions from site-specific approaches that aim at a single defined position. In practice, residue-specific strategies typically target abundant or chemically distinct side chains such as cysteine thiols or lysine amines, enabling modification, labeling, cross-linking, or detection while leaving other residues largely untouched.

In chemistry and bioconjugation, residue-specific reagents include cysteine-reactive compounds that form covalent bonds with thiol groups, such as certain alkylating or Michael-type acceptors, and lysine-targeting reagents like NHS esters that react with primary amines. Other residues can also be targeted with specialized reagents for tyrosine, methionine, or histidine under appropriate conditions. In proteomics and structural biology, residue-specific labeling aids in mapping reactive sites, studying protein interactions, and probing conformational changes without requiring a fixed labeling site.

Residue-specific strategies are contrasted with site-specific approaches, which are designed to modify a single defined position within a protein sequence. While residue-specific methods enable broad reactivity patterns and rapid profiling of residue availability, they can suffer from off-target labeling and context-dependent reactivity. Careful interpretation and appropriate controls are essential to differentiate genuine residue reactivity from nonspecific modification.

See also: site-specific labeling, residue-specific cross-linking, protease specificity, bioconjugation, mass spectrometry.