RESUMO
Five new cyclic peptoids containing (2S,4R)-4-hydroxyproline (Hyp) residues have been designed and synthesized using a mixed "submonomer/monomer" approach. Alkali metal cation affinities and ion transport activities were assessed by experimental (NMR and HPTS assay in liposomes) and computational methods. Easy functionalization of hydroxyproline residues afforded a bouquet of cyclic oligomers showing correlation between ion transport abilities and cytotoxic activities on selected human cancer cell lines.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Hidroxiprolina/química , Peptoides/química , Peptoides/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Sódio/químicaRESUMO
Most of the structural studies made on the secondary structure of peptoids describe their geometric attributes in terms of the classic Ramachandran plot (based on the local analysis of ω, ψ, χ, φ dihedral angles). However, little intuitive understanding is available from internal coordinates when stereochemistry is involved. In this contribution we list all the conformationally stable cyclic peptoids reported up to the year 2017 and propose a simple method to define their geometric arrangement in terms of planar chirality. Evidence of conformational isomerism (due to the long average time of single bond rotation) and conformational chirality (induced by the absence of roto-reflection axes) in this promising class of synthetic macrocycles is provided by NMR spectroscopy (using Pirkle's alcohol as chiral solvating agent) and careful evaluation of X-ray crystallographic studies. The full understanding of the oligomeric macrocycles' structural properties and the clear framing of their conformational isomerism in a proper conceptual scheme is fundamental for future application of peptoids in asymmetric synthesis, chiral recognition and supramolecular chemistry.
