Analogues of both Leu- and Met-enkephalin containing a constrained dipeptide isostere prepared from a Baylis-Hillman adduct.
An efficient route was developed for the synthesis of the Fmoc-protected dipeptide 4, isostere of Gly-Gly containing an alpha-methylene beta-amino acid; the conformationally restricted analogues of Leu-enkephalin, 3a, and Met-enkephalin, 3b, respectively, were prepared by changing 4 for Gly(2)-Gly(3) in the native compounds 3a and 3b whose biological activities were significantly lower than the parent compounds.
Galeazzi
Roberta
R
Dipartimento I.S.A.C., Università Politecnica delle Marche, Via Brecce Bianche, 60131, Ancona, Italy.
Martelli
Gianluca
G
Marcucci
Eleonora
E
Orena
Mario
M
Rinaldi
Samuele
S
Lattanzi
Roberta
R
Negri
Lucia
L
D000595:Amino Acid Sequence; D000818:Animals; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006033:Glycylglycine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D006168:Guinea Pigs; D007082:Ileum; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013237:Stereoisomerism; D014649:Vas Deferens
D004151:Dipeptides; D018377:Neurotransmitter Agents; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D006033:Glycylglycine; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine