1. Academic Validation
  2. Isoform-selective disruption of AKAP-localized PKA using hydrocarbon stapled peptides

Isoform-selective disruption of AKAP-localized PKA using hydrocarbon stapled peptides

  • ACS Chem Biol. 2014 Mar 21;9(3):635-42. doi: 10.1021/cb400900r.
Yuxiao Wang 1 Tienhuei G Ho Daniela Bertinetti Matthias Neddermann Eugen Franz Gary C H Mo Lewis P Schendowich Avinash Sukhu Raybun C Spelts Jin Zhang Friedrich W Herberg Eileen J Kennedy
Affiliations

Affiliation

  • 1 Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia , Athens, Georgia 30602, United States.
Abstract

A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained Peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A Kinase Binding (AKB) domain of several AKAPs were chemically modified to contain an all-hydrocarbon staple and target the docking/dimerization domain of PKA-R, thereby occluding AKAP interactions. The Peptides are cell-permeable against diverse human cell lines, are highly isoform-selective for PKA-RII, and can effectively inhibit interactions between AKAPs and PKA-RII in intact cells. These Peptides can be applied as useful reagents in cell-based studies to selectively disrupt AKAP-localized PKA-RII activity and block AKAP signaling complexes. In summary, the novel hydrocarbon-stapled Peptides developed in this study represent a new class of AKAP disruptors to study compartmentalized RII-regulated PKA signaling in cells.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P2261
    98.39%, PKA-RII破坏剂
    PKA