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 ago 2020
Accepted: 09 set 2020
First published: 21 set 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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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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