Structure-activity analysis of truncated orexin-A analogues at the orexin-1 receptor.
Truncated peptide analogues of orexin-A were prepared and their biological activity assesed at the orexin-1 receptor. Progressive N-terminal deletions identified the minimum C-terminal sequence required for maintaining a significant agonist effect, whilst an alanine scan and other pertinent substitutions identified key side-chain and stereochemical requirements for receptor activation.
Darker
J G
JG
Discovery Chemistry, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. john_darker-1@sbphrd.com
Porter
R A
RA
Eggleston
D S
DS
Smart
D
D
Brough
S J
SJ
Sabido-David
C
C
Jerman
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006224:Cricetinae; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D002118:Calcium