Document Detail

Investigation of 4-(3-hydroxyphenyl)-4-methylpipecolic acid as a conformationally restricted mimic of the tyrosyl residue of leucine-enkephalinamide.
MedLine Citation:
PMID:  3020252     Owner:  NLM     Status:  MEDLINE    
Analogues of leucine-enkephalinamide containing N-terminal cis- or trans-4-(3-hydroxyphenyl)-4-methylpipecolic acid were prepared to examine the conformational requirements of the N-terminal tyrosyl residue in opioid activity. The diastereomeric amino acids were prepared and purified by semipreparative HPLC before incorporation into the peptide. Spectroscopic analysis based on proton nuclear Overhauser enhanced differential spectroscopy (NOEDS) allowed assignment of the cis and trans stereochemistry. Despite spatial analogy between the trans isomer 5 and leucine-enkephalinamide, it possessed neither opioid agonist nor antagonist activity in the guinea pig ileal longitudinal muscle (GPI) or mouse vas deferens (MVD) preparations. Possible explanations for this inactivity are discussed.
E E Sugg; P S Portoghese
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  29     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1986 Oct 
Date Detail:
Created Date:  1986-11-19     Completed Date:  1986-11-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2028-33     Citation Subset:  IM    
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MeSH Terms
Enkephalin, Leucine / analogs & derivatives*,  chemical synthesis,  pharmacology
Magnetic Resonance Spectroscopy
Molecular Conformation
Pipecolic Acids / pharmacology*
Receptors, Opioid / drug effects
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Pipecolic Acids; 0/Receptors, Opioid; 55520-40-6/Tyrosine; 58822-25-6/Enkephalin, Leucine; 60117-24-0/enkephalinamide-Leu

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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