Structure-activity analysis of truncated orexin-A analogues at the orexin-1 receptor

Bioorg Med Chem Lett. 2001 Mar 12;11(5):737-40. doi: 10.1016/s0960-894x(01)00043-9.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium / metabolism*
  • Carrier Proteins / chemical synthesis
  • Carrier Proteins / chemistry*
  • Carrier Proteins / pharmacology*
  • Cricetinae
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neuropeptides / chemical synthesis
  • Neuropeptides / chemistry*
  • Neuropeptides / pharmacology*
  • Orexin Receptors
  • Orexins
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / agonists*
  • Receptors, Neuropeptide / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Carrier Proteins
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Calcium