title: Synthesis and biological activities of linear and cyclic enkephalin analogues containing a psi (E,CH = CH) or psi (CH2CH2) isosteric replacement.
abstract: The peptide CO-NH function was replaced by a trans carbon-carbon double bond or by a CH2-CH2 isostere in enkephalin analogues of DADLE, DCDCE-NH2 or DPDPE. In DADLE the 2-3 and the 3-4 peptide bond was modified, whereas in the cyclic analogues the Gly3-Phe4 bond was replaced by the isosteres Gly psi (E,CH = CH)Phe [5-amino-2-(phenylmethyl)-3(E)-pentenoic acid] or Gly psi (CH2CH2)Phe [5-amino-2-(phenylmethyl)pentanoic acid]. In general, the modification results in a drop in potency which is the largest for the flexible CH2-CH2 replacement. The Gly3 psi (E,CH = CH)Phe4 DCDCE-NH2 analogue retains considerable potency. These results confirm the importance of the peptide function at the 2-3 and 3-4 position in enkephalin analogues for biological potency.
authors.affiliation: Organic Chemistry Unit, Vrije Universiteit Brussel, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Tourwé
authors.forename: J
authors.initials: J
authors.lastname: Couder
authors.forename: M
authors.initials: M
authors.lastname: Ceusters
authors.forename: D
authors.initials: D
authors.lastname: Meert
authors.forename: T F
authors.initials: TF
authors.lastname: Burks
authors.forename: T H
authors.initials: TH
authors.lastname: Kramer
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: R
authors.initials: R
authors.lastname: Knapp
authors.forename: H I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: J E
authors.initials: JE
authors.lastname: Leysen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004745:Enkephalins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004745:Enkephalins; D010456:Peptides, Cyclic; D011957:Receptors, Opioid