Work

Truncated Orexin Peptides: Structure–Activity Relationship Studies

Year: 2013

Type: article

Abstract: Orexin receptors are involved in many processes including energy homeostasis, wake/sleep cycle, metabolism, and reward. Development of potent and selective ligands is an essential step for defining the mechanism(s) underlying such critical processes. The goal of this study was to further investigate the structure–activity relationships of these peptides and to identify the truncated form of the orexin peptides active at OX 1 . Truncation studies have led to OXA (17–33) as the shortest active peptide known to date with a 23-fold selectivity for OX 1 over OX 2 . Alanine, d -amino acid, and proline scans have highlighted the particular importance of Tyr 17, Leu 20, Asn 25, and His 26 for agonist properties of OXA(17–33). The conformation of the C-terminus might also be a defining factor in agonist activity and selectivity of the orexin peptides for the OX 1 receptor.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/ml400333a

Authors: Nadezhda A. German, Ann M. Decker, Brian P. Gilmour, Brian F. Thomas, Yanan Zhang

Institution: RTI International

Language: English

Topic: Sleep and Wakefulness Research

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: green

Funders: Institut National de la Santé et de la Recherche Médicale, National Institute on Drug Abuse

Awards: G1527852770, Orexin-1 Receptor Ligands for Drug Addiction, Orexin-1 Receptor Ligands for Drug Addiction