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A Catch‐and‐Release Approach to Selective Modification of Accessible Tyrosine Residues
Author(s) -
Allan Christopher,
Kosar Miroslav,
Burr Christina V.,
Mackay C. Logan,
Duncan Rory R.,
Hulme Alison N.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800532
Subject(s) - tyrosine , residue (chemistry) , chemistry , surface modification , peptide , combinatorial chemistry , biochemistry , posttranslational modification , chemical modification , amphiphile , stereochemistry , organic chemistry , enzyme , copolymer , polymer
The tyrosine side chain is amphiphilic leading to significant variations in the surface exposure of tyrosine residues in the folded structure of a native sequence protein. This variability can be exploited to give residue‐selective functionalization of a protein substrate by using a highly reactive diazonium group tethered to an agarose‐based resin. This novel catch‐and‐release approach to protein modification has been demonstrated for proteins with accessible tyrosine residues, which are compared with a control group of proteins in which there are no accessible tyrosine residues. MS analysis of the modified proteins showed that functionalization was highly selective, but reactivity was further attenuated by the electrostatic environment of any individual residue. Automated screening of PDB structures allows identification of potential candidates for selective modification by comparison with the accessibility of the tyrosine residue in a benchmark peptide (GYG).