Reductive alkylation of lysine residues to change protein properties (pI, solubility and hydropathy) which may promote crystallization via improved crystal packing.

Reductive alkylation of proteins has been successfully applied to obtain a significant number of high-quality crystals from proteins previously unable to be crystallized. Alkylating the e amino group of lysines alters the hydropathy, solubility and pI of the protein which may promote crystallization by altering sample-sample, sample-solvent and crystal packing interactions.

Reductive alkylation does not change the intrinsic charge on a protein but may change the isoelectric point (pI) slightly. The N-terminal amino group on the backbone will also be reductively alkylated. In general, alkylated proteins retain their original biochemical function. This protocol is designed with the goal of generating a high degree of modification with few side reactions, resulting in a homogeneous population of protein.