[D-Ala2]-deltorphin I peptoid and retropeptoid analogues: synthesis, biological activity and conformational investigations

✍ Scribed by Laura Biondi; Elisa Giannini; Fernando Filira; Marina Gobbo; Lucia Negri; Raniero Rocchi

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 137 KB
• Volume: 10
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.566

✦ Synopsis

Abstract

The synthesis is described of a [D‐Ala^2^]‐deltorphin I peptoid analogue in which all amino acid residues have been substituted by the corresponding N‐alkylglycine residues. The [D‐Ala^2^]‐deltorphin I retropeptoid was also prepared as well as [Ala^1^,D‐Ala^2^]‐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‐Ala^2^]‐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 δ‐ and µ‐opioids, respectively. Measurements of CD in the presence of β‐cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the [Ntyr^1^,D‐Ala^2^]‐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. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.