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N ε ‐(thiaprolyl)‐lysine as a handle for site‐specific protein conjugation
Author(s) -
Van de Vijver Pieter,
Suylen Dennis,
Dirksen Anouk,
Dawson Philip E.,
Hackeng Tilman M.
Publication year - 2010
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21485
Subject(s) - chemistry , lysine , thiol , disulfide bond , hydroxylamine , residue (chemistry) , combinatorial chemistry , bioconjugation , peptide , side chain , chemical modification , stereochemistry , autoxidation , chemical ligation , native chemical ligation , cysteine , polymer chemistry , amino acid , organic chemistry , biochemistry , polymer , enzyme
In this article, we introduce the use of a thiaproline‐modified lysine side‐chain [Lys(Thz)], as an unlockable handle that enables late‐stage, site‐selective modification of chemically synthesized proteins. The Lys(Thz) residue was incorporated into the murine chemokine RANTES to demonstrate its compatibility with Boc/Bzl solid phase peptide synthesis, native chemical ligation, and disulfide bond formation. After oxidative folding of the protein, the thiol was liberated under mild reaction conditions [0.2 M hydroxylamine (NH 2 OH) or O ‐methylhydroxylamine (MeONH 2 ), pH 4] and was subsequently reacted with thiol‐selective tags. This side chain protection strategy enables the use of readily available thiol‐reactive probes for the modification of internally disulfide bonded proteins. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 465–474, 2010.
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