RESUMEN
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.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Hidroxiprolina/química , Peptoides/química , Peptoides/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Sodio/químicaRESUMEN
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.
Asunto(s)
Peptoides/química , Cristalografía por Rayos X , Modelos Moleculares , Conformación Proteica , EstereoisomerismoRESUMEN
An efficient protocol for the solid-phase synthesis of six members of a new class of extended macrocyclic peptoids (based on ortho-, meta- and para-N-(methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3-5) and tetramers (6-8) demonstrate that annulation of the rigidified peptoids can generate new hosts with the ability to sequestrate one or two sodium cations with the affinities and stoichiometries defined by the macrocycle morphology. Ion transport studies have been also performed in order to better appreciate the factors promoting transmembrane cation translocation.
Asunto(s)
Compuestos de Bencilo/síntesis química , Ionóforos/síntesis química , Compuestos Macrocíclicos/síntesis química , Peptoides/síntesis química , Compuestos de Bencilo/química , Ciclización , Transporte Iónico , Ionóforos/química , Compuestos Macrocíclicos/química , Modelos Moleculares , Peptoides/química , Sodio/químicaRESUMEN
This chapter covers the synthetic aspects of both linear or cyclic peptides and depsipeptides isolated from opisthobranch molluscs. In many cases, synthetic effort not only determined the absolute stereostructure of these compounds but also made it possible to supply sufficient amounts for the evaluation of pharmacological activities. A summary of the synthetic work associated with each compound is reported after a short description of its natural source and biological properties. Discussion in the text concentrates on key reactions and synthetic efficiency.