Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation

Daniel Clayton; Sameer S. Kulkarni; Jessica Sayers; Luke J. Dowman; Jorge Ripoll-Rozada; Pedro José Barbosa Pereira; Richard J. Payne

doi:10.1039/D0CB00146E

Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation†

Daniel Clayton,^a Sameer S. Kulkarni,^a Jessica Sayers,^a Luke J. Dowman,^a Jorge Ripoll-Rozada,

^b Pedro José Barbosa Pereira

^b and Richard J. Payne

*^ac

Author affiliations

* Corresponding authors

^a School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia
E-mail: richard.payne@sydney.edu.au

^b IBMC – Instituto de Biologia Molecular e Celular & Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal

^c Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, NSW 2006, Australia

Abstract

The haemathrins are tick-derived thrombin-inhibiting proteins predicted to be post-translationally sulfated. This study reports the ligation-based assembly of eight homogeneously sulfated variants of haemathrin-1 and haemathrin-2. Functional assays revealed a two orders-of-magnitude enhancement in thrombin-inhibitory potency by tyrosine sulfation, thus reinforcing the crucial role of this post-translational modification for the activity of anticoagulant proteins.

This article is part of the themed collection: The Chemical Biology of Peptides

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DOI: https://doi.org/10.1039/D0CB00146E
Article type: Communication
Submitted: 10 Aug 2020
Accepted: 09 Sep 2020
First published: 21 Sep 2020
This article is Open Access

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RSC Chem. Biol., 2020,1, 379-384

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Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation

D. Clayton, S. S. Kulkarni, J. Sayers, L. J. Dowman, J. Ripoll-Rozada, P. J. B. Pereira and R. J. Payne, RSC Chem. Biol., 2020, 1, 379 DOI: 10.1039/D0CB00146E

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RSC Chemical Biology

Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation†

Abstract

Supplementary files

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Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation

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