title: Targeting protein-protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease.
abstract: The cAMP signaling system can trigger precise physiological cellular responses that depend on the fidelity of many protein-protein interactions, which act to bring together signaling intermediates at defined locations within cells. In the heart, cAMP participates in the fine control of excitation-contraction coupling, hence, any disregulation of this signaling cascade can lead to cardiac disease. Due to the ubiquitous nature of the cAMP pathway, general inhibitors of cAMP signaling proteins such as PKA, EPAC and PDEs would act non-specifically and universally, increasing the likelihood of serious 'off target' effects. Recent advances in the discovery of peptides and small molecules that disrupt the protein-protein interactions that underpin cellular targeting of cAMP signaling proteins are described and discussed.
authors.affiliation: Institute of Cardiovascular & Medical Science, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Louisa C Y
authors.initials: LC
authors.lastname: Lee
authors.forename: Donald H
authors.initials: DH
authors.lastname: Maurice
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D060066:Protein Interaction Maps / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D010455:Peptides; D054852:Small Molecule Libraries; D000242:Cyclic AMP