Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display

J. Johansen-Leete; T. Passioura; T. Passioura; T. Passioura; T. Passioura; S.R. Foster; R.P. Bhusal; D.J. Ford; M. Liu; S.A.K. Jongkees; H. Suga; M.J. Stone; R.J. Payne; R.J. Payne

doi:10.1021/jacs.0c03152

Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display

J. Johansen-Leete, T. Passioura, T. Passioura, T. Passioura, T. Passioura, S.R. Foster, R.P. Bhusal, D.J. Ford, M. Liu, S.A.K. Jongkees, H. Suga, M.J. Stone, R.J. Payne, R.J. Payne

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

© 2020 American Chemical Society.Targeting chemokine signaling is an attractive avenue for the treatment of inflammatory disorders. Tyrosine sulfation is an important post-translational modification (PTM) that enhances chemokine-receptor binding and is also utilized by a number of pathogenic organisms to improve the binding affinity of immune-suppressive chemokine binding proteins (CKBPs). Here we report the display selection of tyrosine-sulfated cyclic peptides using a reprogrammed genetic code to discover high-affinity ligands for the chemokine CCL11 (eotaxin-1). The selected cyclic sulfopeptides possess high affinity for the target chemokine (as well as one or more of the related family members CCL2, CCL7 and CCL24) and inhibit CCL11 activation of CC chemokine receptor 3 (CCR3). This work demonstrates the utility of exploiting native PTMs as binding motifs for the generation of new leads for medicinal chemistry.

Original language	English
Pages (from-to)	9141-9146
Journal	Journal of the American Chemical Society
Volume	142
Issue number	20
DOIs	https://doi.org/10.1021/jacs.0c03152
Publication status	Published - 20 May 2020
Externally published	Yes

Funding

We acknowledge funding from the National Health and Medical Research Council (Investigator Grant APP1174941, Project Grant APP1140867 to M.J.S. and R.J.P. and APP1140874 to M.J.S.) and the Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant Agreement 746631 (to S.A.K.J.).

Funders	Funder number
Horizon 2020 Framework Programme
National Health and Medical Research Council	APP1140874, APP1140867, APP1174941
Horizon 2020	746631

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Johansen-Leete, J., Passioura, T., Passioura, T., Passioura, T., Passioura, T., Foster, S. R., Bhusal, R. P., Ford, D. J., Liu, M., Jongkees, S. A. K., Suga, H., Stone, M. J., Payne, R. J., & Payne, R. J. (2020). Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display. Journal of the American Chemical Society, 142(20), 9141-9146. https://doi.org/10.1021/jacs.0c03152

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title = "Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display",

abstract = "{\textcopyright} 2020 American Chemical Society.Targeting chemokine signaling is an attractive avenue for the treatment of inflammatory disorders. Tyrosine sulfation is an important post-translational modification (PTM) that enhances chemokine-receptor binding and is also utilized by a number of pathogenic organisms to improve the binding affinity of immune-suppressive chemokine binding proteins (CKBPs). Here we report the display selection of tyrosine-sulfated cyclic peptides using a reprogrammed genetic code to discover high-affinity ligands for the chemokine CCL11 (eotaxin-1). The selected cyclic sulfopeptides possess high affinity for the target chemokine (as well as one or more of the related family members CCL2, CCL7 and CCL24) and inhibit CCL11 activation of CC chemokine receptor 3 (CCR3). This work demonstrates the utility of exploiting native PTMs as binding motifs for the generation of new leads for medicinal chemistry.",

author = "J. Johansen-Leete and T. Passioura and T. Passioura and T. Passioura and T. Passioura and S.R. Foster and R.P. Bhusal and D.J. Ford and M. Liu and S.A.K. Jongkees and H. Suga and M.J. Stone and R.J. Payne and R.J. Payne",

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Johansen-Leete, J, Passioura, T, Passioura, T, Passioura, T, Passioura, T, Foster, SR, Bhusal, RP, Ford, DJ, Liu, M, Jongkees, SAK, Suga, H, Stone, MJ, Payne, RJ & Payne, RJ 2020, 'Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display', Journal of the American Chemical Society, vol. 142, no. 20, pp. 9141-9146. https://doi.org/10.1021/jacs.0c03152

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AU - Johansen-Leete, J.

AU - Passioura, T.

AU - Foster, S.R.

AU - Bhusal, R.P.

AU - Ford, D.J.

AU - Liu, M.

AU - Jongkees, S.A.K.

AU - Suga, H.

AU - Stone, M.J.

AU - Payne, R.J.

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AB - © 2020 American Chemical Society.Targeting chemokine signaling is an attractive avenue for the treatment of inflammatory disorders. Tyrosine sulfation is an important post-translational modification (PTM) that enhances chemokine-receptor binding and is also utilized by a number of pathogenic organisms to improve the binding affinity of immune-suppressive chemokine binding proteins (CKBPs). Here we report the display selection of tyrosine-sulfated cyclic peptides using a reprogrammed genetic code to discover high-affinity ligands for the chemokine CCL11 (eotaxin-1). The selected cyclic sulfopeptides possess high affinity for the target chemokine (as well as one or more of the related family members CCL2, CCL7 and CCL24) and inhibit CCL11 activation of CC chemokine receptor 3 (CCR3). This work demonstrates the utility of exploiting native PTMs as binding motifs for the generation of new leads for medicinal chemistry.

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DO - 10.1021/jacs.0c03152

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JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 20

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Discovery of Potent Cyclic Sulfopeptide Chemokine Inhibitors via Reprogrammed Genetic Code mRNA Display

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