Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues

L.J. Dowman, Stijn Agten, J. Ripoll-Rozada, Bárbara Calisto, P.J.B. Pereira, R.J. Payne*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Tyrosine sulfation is an important post-translational modification of peptides and proteins which underpins and modulates many protein-protein interactions. In order to overcome the inherent instability of the native modification, we report the synthesis of two sulfonate analogues and their incorporation into two thrombin-inhibiting sulfopeptides. The effective mimicry of these sulfonate analogues for native sulfotyrosine was validated in the context of their thrombin inhibitory activity and binding mode, as determined by X-ray crystallography.

Original languageEnglish
Pages (from-to)10923-10926
Number of pages4
JournalChemical Communications
Volume57
Issue number83
DOIs
Publication statusPublished - 19 Oct 2021
Externally publishedYes

Keywords

  • TYROSINE SULFATION
  • ANTICOAGULANT
  • SULFOPEPTIDES
  • SULFOPROTEINS
  • RECOGNITION
  • REVEALS
  • BINDING
  • SALIVA

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