title: Design of a peptide inhibitor of tyrosine kinase 2.
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 binding domain of the kinase, potentially limiting efficacy and selectivity. The development of antisense peptide inhibitors is a relatively unexplored area of research, and here we investigate inhibitory peptides 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 for TYK2-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.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Works
authors.forename: Benben
authors.initials: B
authors.lastname: Song
authors.forename: Patrick
authors.initials: P
authors.lastname: Kibler
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Tanga
authors.forename: Amit K
authors.initials: AK
authors.lastname: Galande
authors.affiliation: Center for Immunology and Infectious Diseases, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park CA 94025, USA. annalisa.dandrea@sri.com.
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Andrea
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D010455:Peptides; D047428:Protein Kinase Inhibitors; D053634:TYK2 Kinase