Selective and Reversible Photochemical Derivatization of Cysteine Residues in Peptides and Proteins

• Published in: Chemical science (Cambridge) Vol. 5; no. 4; pp. 1591 - 1598
• Main Authors: Arumugam, Selvanathan, Guo, Jun, Mbua, Ngalle Eric, Friscourt, Frédéric, Lin, Nannan, Nekongo, Emmanuel, Boons, Geert-Jan, Popik, Vladimir V
• Format: Journal Article
• Language: English
• Published: England 01.04.2014
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c3sc51691a

Selective derivatization of solvent-exposed cysteine residues in peptides and proteins is achieved by brief irradiation of an aqueous solution containing 3-(hydroxymethyl)-2-naphthol derivatives (NQMPs) with 350 nm fluorescent lamp. NQMP can be conjugated with various moieties, such as PEG, dyes, carbohydrates, or possess a fragment for further selective derivatization, e.g., biotin, azide, alkyne, etc. Attractive features of this labeling approach include an exceptionally fast rate of the reaction and a requirement for low equivalence of the reagent. The NQMP-thioether linkage is stable under ambient conditions, survives protein digestion and MS analysis. Irradiation of NQMP-labeled protein in a dilute solution (<40 μM) or in the presence of a vinyl ether results in a traceless release of the substrate. The reversible biotinylation of bovine serum albumin, as well as capture and release of this protein using NeutrAvidin Agarose resin beads has been demonstrated.