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Biomedical sciences publications May 1, 2014 Article

Design of a Peptide Inhibitor of Tyrosine Kinase 2

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Works, M. G., Song, B., Kibler, P., Tanga, M. J., Galande, A. K., & D’Andrea, A. (2014). Design of a peptide inhibitor of tyrosine kinase 2. Protein and Peptide Letters, 21(5), 419-425.

Abstract

Tyrosine kinase inhibitors show great promise as clinical therapies, but small molecule inhibitors that are available in the clinic and under development bind to the adenosine triphosphate bindingdomain of the kinase, potentially limiting efficacy and selectivity. The development of antisensepeptide inhibitors is a relatively unexplored area of research, and here we investigate inhibitorypeptides specific for the Janus-associated kinase (JAK) family member, tyrosine kinase 2 (TYK2). We have developed peptides that are 2-3 times more selective for TYK2 than other JAK family members, with a TYK2 IC50 of 1.2 μM. In addition, TYK2 inhibitory peptides show specificity forTYK2-mediated functions over JAK1 functions in cell-based assays. These peptides provide a new tool for the development of specific peptide inhibitors for closely related tyrosine kinases.

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