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

Abstract

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.

Peptoid–Peptide Hybrid Backbone Architectures

“…[145] The initial papers regarding mass spectrometric comparisons of peptides, peptoids, and peptoid-peptide hybrids revealed signature fragmentation patterns for peptoid residues that were not observed in peptides, [137][138][139] and more recently partial Edman degradation (PED) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry were combined to efficiently sequence peptoidpeptide hybrids from one-bead-one-compound combinatorial libraries. [140] Finally, Wessjohann and co-workers have reported [117] B) d-opiod receptor ligand, Rocchi and co-workers; [120][121][122] C) analogues of the trypsin inhibitor SIFT-1, Rolka and co-workers. [125] 156 www.chembiochem.org Ugi multicomponent reactions that furnished selenocysteine containing peptoids.…”

“…[119] In a series of papers by Rocchi and co-workers, peptoid-substituted compounds based on dermorphin, deltorphin, and endomorphin peptides were investigated as opioid receptor agonists (14, Scheme 4). [120][121][122] Protease inhibitors containing single peptoid substitutions based on simplified analogues of the trypsin inhibitor SFTI-1 have been reported. [123][124][125] Two such candidates (15, Scheme 4) showed either improved or unchanged inhibitory activity against the enzymes tested.…”

Solid-Phase Synthesis of N-Substituted Glycine Oligomers (α‑Peptoids) and Derivatives

“…There exists a range of cleavage cocktails based on TFA (trifluoroacetic acid) ( Table 10 ) where the most common system is TFA:TIS:water (95:2.5:2.5 (v/v), TIS is triisopropylsilane) for 1-2 hours at room temperature. Other scavengers are thioanisole [ 42 , 88 , 98 ]; anisole [ 52 , 71 ]; TES (triethylsilane) [ 61 , 65 , 101 ]; phenol [ 130 ]; m -cresol [ 87 ] and EDT (ethylenedithiol) [ 88 , 98 ]. Longer deprotection times are used when side-chain protecting groups are present [ 80 , 130 ].…”

Convenient preparation of deuterium‐labeled analogs of peptides containing N‐substituted glycines for a stable isotope dilution LC‐MS quantitative analysis

“…The term peptomer was proposed by Østergaard and Holm from pep tide–pep to id hybrid poly mers . A shift of the amino acid side chains from the α ‐carbon to the backbone nitrogen, yielding NSG derivatives, opened a wider possibility of investigation of many biological effects . Because of their unlimited structural diversity and functional versatility, NSGs are widely used as non‐chiral building blocks and molecular scaffolds in constructing combinatorial libraries of bioactive compounds .…”