Open AccessPEGylation near a Patch of Nonpolar Surface Residues Increases the Conformational Stability of the WW Domain
Author(s) -
Steven R. E. Draper,
Dallin S Ashton,
Benjamin M Conover,
Anthony J Carter,
K.L. Stern,
Qiang Xiao,
Joshua L. Price
Publication year - 2019
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.9b02615
Subject(s) - pegylation , azide , chemistry , cycloaddition , biophysics , stereochemistry , catalysis , organic chemistry , biology , polyethylene glycol
Many proteins have one or more surface-exposed patches of nonpolar residues; our observations here suggest that PEGylation near such locations might be a useful strategy for increasing protein conformational stability. Specifically, we show that conjugating a PEG-azide to a propargyloxyphenylalanine via the copper(I)-catalyzed azide-alkyne cycloaddition can increase the conformational stability of the WW domain due to a favorable synergistic effect that depends on the hydrophobicity of a nearby patch of nonpolar surface residues.