Endomorphin-1 analogs containing α-methyl-β-amino acids exhibit potent analgesic activity after peripheral administration

Yuan Wang; Junxian Yang; Xin Liu; Long Zhao; Dongxu Yang; Jingjing Zhou; Dan Wang; Lingyun Mou; Rui Wang

doi:10.1039/c7ob01115f

Endomorphin-1 analogs containing α-methyl-β-amino acids exhibit potent analgesic activity after peripheral administration

Org Biomol Chem. 2017 Jun 14;15(23):4951-4955. doi: 10.1039/c7ob01115f.

Authors

Yuan Wang¹, Junxian Yang, Xin Liu, Long Zhao, Dongxu Yang, Jingjing Zhou, Dan Wang, Lingyun Mou, Rui Wang

Affiliation

¹ Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Department of Pharmacology, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, P. R. China. [email protected].

PMID: 28567467
DOI: 10.1039/c7ob01115f

Abstract

This study describes the design and synthesis of endomorphin-1 analogs containing C-terminal aromatic α-methyl-β-amino acids and an N-terminal native tyrosine or 2,6-dimethyl-tyrosine. We show that, in comparison with the parent peptide, these analogs exhibit improved bioactivity and blood-brain barrier penetration after intravenous administration, and have a lower tendency to induce constipation and sedation than morphine.

MeSH terms

Administration, Intravenous
Amino Acids / chemistry*
Analgesics / administration & dosage
Analgesics / chemistry*
Analgesics / metabolism
Analgesics / pharmacology*
Animals
Blood-Brain Barrier / metabolism
Methylation
Mice
Oligopeptides / administration & dosage
Oligopeptides / chemistry*
Oligopeptides / metabolism
Oligopeptides / pharmacology*

Substances

Amino Acids
Analgesics
Oligopeptides
endomorphin 1