Increasing the kinase specificity of k252a by protein surface recognition

Tanya L Schneider; Rebecca S Mathew; Kevin P Rice; Kazuhiko Tamaki; John L Wood; Alanna Schepartz

doi:10.1021/ol050179o

Increasing the kinase specificity of k252a by protein surface recognition

Org Lett. 2005 Apr 28;7(9):1695-8. doi: 10.1021/ol050179o.

Authors

Tanya L Schneider¹, Rebecca S Mathew, Kevin P Rice, Kazuhiko Tamaki, John L Wood, Alanna Schepartz

Affiliation

¹ Department of Chemistry and Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8107, USA.

PMID: 15844883
DOI: 10.1021/ol050179o

Abstract

[reaction: see text] Here we describe a miniature protein (1) that presents the cAMP-dependent protein kinase (PKA) recognition epitope found within the heat-stable Protein Kinase Inhibitor protein (PKI) and a miniature protein conjugate (1-K252a) in which 1 is joined covalently to the high-affinity but nonselective kinase inhibitor K252a. Miniature protein 1 recognizes PKA with an affinity that rivals that of PKI and, in the context of 1-K252a, leads to a dramatic increase in kinase specificity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Carbazoles / chemistry
Carbazoles / pharmacology*
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases / metabolism*
Indole Alkaloids
Intracellular Signaling Peptides and Proteins*
Molecular Structure
Substrate Specificity

Substances

Carbazoles
Indole Alkaloids
Intracellular Signaling Peptides and Proteins
protein kinase modulator
staurosporine aglycone
Cyclic AMP-Dependent Protein Kinases

Grants and funding

GM 65453/GM/NIGMS NIH HHS/United States