Targeting biomolecules with reversible covalent chemistry.
Interaction of biomolecules typically proceeds in a highly selective and reversible manner, for which covalent bond formation has been largely avoided due to the potential difficulty of dissociation. However, employing reversible covalent warheads in drug design has given rise to covalent enzyme inhibitors that serve as powerful therapeutics, as well as molecular probes with exquisite target selectivity. This review article summarizes the recent advances in the development of reversible covalent chemistry for biological and medicinal applications. Specifically, we document the chemical strategies that allow for reversible modification of the three major classes of nucleophiles in biology: thiols, alcohols and amines. Emphasis is given to the chemical mechanisms that underlie the development of these reversible covalent reactions and their utilization in biology.
Department of Chemistry, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, United States.
Anupam
A
Bandyopadhyay
Department of Chemistry, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, United States. Electronic address: jianmin.gao@bc.edu.
Jianmin
J
Gao
D000178:Acrylamides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D007700:Kinetics
D000178:Acrylamides; D000588:Amines