[D-Ala2]-Deltorphin I peptoid and retropeptoid analogues: synthesis, biological activity and conformational investigations.
The synthesis is described of a [D-Ala2]-deltorphin I peptoid analogue in which all amino acid residues have been substituted by the corresponding N-alkylglycine residues. The [D-Ala2]-deltorphin I retropeptoid was also prepared as well as [Ala1 ,D-Ala2]-deltorphin 1 and the corresponding peptoid. Structural investigations by FT-IR and fluorescence measurements were carried out on the synthetic analogues and on some [D-Ala2]-deltorphin 1 peptide-peptoid hybrids previously prepared. According to the fluorescence measurements the distance between the aromatic residues in the deltorphin I peptoid and retropeptoid is similar to that suggested for the delta- and micro-opioids, respectively. Measurements of CD in the presence of beta-cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the [Ntyr1,D-Ala2]-deltorphin I, but an increasing dichroic effect appears in the spectra of both the deltorphin I peptoid and retropeptoid. Activity tests on isolated organ preparations showed that the modifications made produced a dramatic decrease in the agonistic activity of the synthetic derivatives.
Biondi
Laura
L
Department of Organic Chemistry, University of Padova, Institute of Biomolecular Chemistry, CNR, Section of Padova, via Marzolo, 1, 35131 Padova, Italy.
Giannini
Elisa
E
Filira
Fernando
F
Gobbo
Marina
M
Negri
Lucia
L
Rocchi
Raniero
R
D019943:Amino Acid Substitution; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009294:Narcotics / Q000138:chemical synthesis / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D034444:Peptoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology
D009294:Narcotics; D009842:Oligopeptides; D034444:Peptoids; D047392:beta-Cyclodextrins; C060208:deltorphin I, Ala(2)-