RFamide Peptides Structure, Function, Mechanisms and Pharmaceutical Potential 英文参考文献.docVIP

Pharmaceuticals 2011, 4, 1248-1280; doi:10.3390/ph4091248 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review RFamide Peptides: Structure, Function, Mechanisms and Pharmaceutical Potential Maria Findeisen ?, Daniel Rathmann ? and Annette G. Beck-Sickinger * Institute of Biochemistry, Leipzig University, Brüderstra?e 34, 04103 Leipzig, Germany; E-Mails: mfind@uni-leipzig.de (M.F.); rathmann@uni-leipzig.de (D.R.) ? These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: beck-sickinger@uni-leipzig.de; Tel.: +49-341-9736900; Fax: +49-341-9736909. Received: 29 August 2011; in revised form: 9 September 2011 / Accepted: 15 September 2011 / Published: 21 September 2011 Abstract: Different neuropeptides, all containing a common carboxy-terminal RFamide sequence, have been characterized as ligands of the RFamide peptide receptor family. Currently, five subgroups have been characterized with respect to their N-terminal sequence and hence cover a wide pattern of biological functions, like important neuroendocrine, behavioral, sensory and automatic functions. The RFamide peptide receptor family represents a multiligand/multireceptor system, as many ligands are recognized by several GPCR subtypes within one family. Multireceptor systems are often susceptible to cross-reactions, as their numerous ligands are frequently closely related. In this review we focus on recent results in the field of structure-activity studies as well as mutational exploration of crucial positions within this GPCR system. The review summarizes the reported peptide analogs and recently developed small molecule ligands (agonists and antagonists) to highlight the current understanding of the pharmacophoric elements, required for affinity and activity at the receptor family. Furthermore, we address the biolo