Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile.
Amino Acid Sequence
Amino Acid Substitution
Animals
Apelin Receptors
/ chemistry
Blood Pressure
/ drug effects
GTP-Binding Protein alpha Subunits, G12-G13
/ chemistry
Half-Life
Humans
Intercellular Signaling Peptides and Proteins
/ chemistry
Male
Protein Binding
Protein Stability
Rats
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
13 05 2021
13 05 2021
Historique:
pubmed:
2
2
2021
medline:
17
6
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
Side-chain-constrained amino acids are useful tools to modulate the biological properties of peptides. In this study, we applied side-chain constraints to apelin-13 (Ape13) by substituting the Pro12 and Phe13 positions, affecting the binding affinity and signaling profile on the apelin receptor (APJ). The residues 1Nal, Trp, and Aia were found to be beneficial substitutions for Pro12, and the resulting analogues displayed high affinity for APJ (
Identifiants
pubmed: 33524256
doi: 10.1021/acs.jmedchem.0c01941
doi:
Substances chimiques
Apelin Receptors
0
Intercellular Signaling Peptides and Proteins
0
apelin-13 peptide
0
GTP-Binding Protein alpha Subunits, G12-G13
EC 3.6.5.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5345-5364Subventions
Organisme : CIHR
Pays : Canada