Synthesis and pharmacological evaluation of new biomimetic peptides and benzothiadiazins
type: Dataset
description: ATP-sensitive potassium channels (KATP) play an important role in many cellular processes. The modulation of these channels by activating molecules may constitute very interesting pharmacological and medicinal applications. For this purpose, we have designed and synthesized new hybrid molecules cromakalim-diazoxide and diazoxide-amine/aminoacid. We also evaluated the relaxant activity of these compounds on aorta of rats. The obtained results do not show a significant relaxant effect. Studies on other tissues, including pancreatic  cells and uterine muscle, are envisaged to explore the potency of these compounds and their possible tissue selectivity.Otherwise, Protein-protein interactions play a fundamental role in almost all cellular processes. They are strongly involved in the formation of the dimeric structure of HIV-1 protease and β amyloid peptide aggregation involved in Alzheimer's disease. Inhibition of these interactions would be a therapeutic advantage for the treatment of AIDS and Alzheimer's disease. We designed and synthesized on one hand, molecular tongs based on carbonylhydrazide oligohydrazid (Azatide) fragments and in the other hand, pentapeptide molecules with a central fluorinated and hydroxylated aminoacid. Finally, we tested the ability of molecular tongs to disrupt the terminal β sheet of the HIV-1 PR to inhibit its dimerization and thus its activity. We have also conducted a structure-activity relationship study and According to the results it seems that flexibility is detrimental to the inhibitory activity. We evaluated as well the ability of new fluorinated and hydroxylated peptidomimetics to accelerate or inhibit the aggregation of Aβ1-42 peptide in order to reduce the presence of small toxic oligomers. The results are very promising that we succeeded in developing a pentapeptide able to completely inhibit the aggregation of Aβ1-42, and in the other hand pseudopentapeptides able to accelerate its aggregation. We also demonstrated the influen…
identifier: NNT: 2013PA114804
issued: 2026-05-07T03:53:36.802135
language: fr
modified: 2026-05-07T03:53:36.802139
contact point: Organization
  fn: CCSD
keyword: activite-myorelaxante
keyword: aggregation
keyword: agregation
keyword: aids
keyword: alzheimers-disease
keyword: amine
keyword: aminoacide
keyword: amyloid-peptide
keyword: azatide
keyword: canaux-katp
keyword: carbonylhydrazides
keyword: chimothechemical-sciencesother
keyword: cromakalim
keyword: diazoxide
keyword: dimerisation
keyword: dimerization
keyword: feuillet
keyword: fluorinated-and-hydroxylated-peptidomimetics
keyword: hiv-1-protease
keyword: infoeu-reposemanticsdoctoralthesis
keyword: interactions-proteine-proteine
keyword: katp-channels
keyword: maladie-dalzheimer
keyword: motif-alcool-fluore
keyword: muscle-relaxant-activity
keyword: peptide--amyloide
keyword: peptidomimetique
keyword: protease-du-vih-1
keyword: protein-interactions
keyword: sheet
keyword: sida
keyword: theses
landing page: https://theses.hal.science/tel-00940587

Synthesis and pharmacological evaluation of new biomimetic peptides and benzothiadiazins
type: Distribution
format: HTML
issued: 2026-05-07T03:53:36.804399
modified: 2026-05-07T03:53:36.774207
access URL: https://theses.hal.science/tel-00940587

test_moissonnage_selune
type: Agent