Open AccessTruncated Orexin Peptides: Structure–Activity Relationship Studies
Author(s) -
Nadezhda German,
Ann M. Decker,
Brian P. Gilmour,
Brian F. Thomas,
Yanan Zhang
Publication year - 2013
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml400333a
Subject(s) - orexin a , orexin , computational biology , chemistry , biochemistry , neuropeptide , biology , receptor
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 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.