title: G-protein-directed ligand discovery with peptide combinatorial libraries.
abstract: Modulators of G-protein signaling have a central role in controlling cell physiology and represent over half of all marketed prescription drugs. G-protein pathways have traditionally been targeted by developing ligands to the extracellular surface of a small subset of the estimated approximately 1000 G-protein-coupled receptors in humans. The intracellular machinery, consisting of the cytosolic receptor surfaces and heterotrimeric G proteins, provides an equivalent diversity of targets that has remained relatively unexplored until now. This review summarizes recent efforts using combinatorial peptide libraries to develop new G-protein signaling modulators targeting intracellular components.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Ja
authors.forename: Richard W
authors.initials: RW
authors.lastname: Roberts
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger; D020239:Receptor Cross-Talk; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins