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Deorphanization of novel peptides and their receptors Ozawa A; Lindberg I; Roth B; Kroeze WKAAPS J 2010[Sep]; 12 (3): 378-84Peptide hormones and neuropeptides play important roles in endocrine and neural signaling, often using G protein-coupled receptor (GPCR)-mediated signaling pathways. However, the rate of novel peptide discovery has slowed dramatically in recent years. Genomic sequencing efforts have yielded a large number of cDNA sequences that potentially encode novel candidate peptide precursors, as well as hundreds of orphan GPCRs with no known cognate ligands. The complexity of peptide signaling is further highlighted by the requirement for specific posttranslational processing steps, and these must be accomplished in vitro prior to testing newly discovered peptide precursor candidates in receptor assays. In this review, we present historic as well as current approaches to peptide discovery and GPCR deorphanization. We conclude that parallel and combinatorial discovery methods are likely to represent the most fruitful avenues for both peptide discovery as well as for matching the remaining GPCRs with their peptide ligands.|Combinatorial Chemistry Techniques[MESH]|Computational Biology[MESH]|Mass Spectrometry[MESH]|Peptides/*physiology[MESH]|Protein Processing, Post-Translational[MESH]|Receptors, Cell Surface/*physiology[MESH] |
