N-epsilon-(Thiaprolyl)-lysine as a Handle for Site-Specific Protein Conjugation

Pieter Van de Vijver, Dennis P. Suylen, Anouk Dirksen, Philip E. Dawson, Tilman M. Hackeng*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 [0.2M hydroxylamine (NH2OH) or O-methylhydroxylamine (MeONH2), 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.
Original languageEnglish
Pages (from-to)465-474
Issue number4
Publication statusPublished - 2010


  • synthesized proteins
  • chemokine
  • peptide synthesis


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