Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic oligolactam analogues show a correlation between ion transport abilities in artificial liposomes and cytotoxic activity on human cancer cell lines. The reported results demonstrate that the versatile cyclic peptoid scaffold, for its remarkable conformational and complexing properties, can morphologically mimic related natural products and elicit powerful biological activities

Structure - Bioactivity Relationship in Cyclic Peptoids: An Overview

Cyclic N-substituted glycines oligomers, also known as cyclic peptoids, constitute a promising class of novel peptidomimetics, capable of simulating bioactive effectors with enhanced proteolytical stability and cell permeability as crucial bonuses. The macrocyclic constraint, essential for the induction of stable secondary structures, determines the biomimetic potential of such molecules, which act as antimicrobials, cytotoxic agents, siderophores, glycosidases inhibitors and so on. The bioactivity can be either attributed to the macrocyclic core (especially chelation) or to the side-chains (when endowed with specific groups or pharmacophores). The structure-bioactivity correlations emerging for this class of peptidomimetics, based on the study of conformational order and morphology of the backbone architecture, unravel interesting avenues for the rational design of more effective cyclooligomeric biomimics

NHC-Gold(I) complexes active in phenylacetylene hydroamination

Imines are key molecules for the synthesis of several N-containing compounds of industrial interest. The hydroamination reaction represents an excellent green strategy to build C-N bonds by adding amines to multiple carbon bonds with a 100% atom economy. The addition of amines to double and triple carbon bonds requires very high activation barriers, but transition metal complexes can be used to activate multiple C-C bonds.1 Recently, NHC-gold complexes were shown to be able to promote hydroamination of alkynes.2 Herein we present highly regioselective Markovnikov hydroaminations of phenylacetylene with arylamines in the presence of different N-Heterocyclic gold(I) complexes (Figure 1). The best reaction conditions were identified by screening co-catalysts and solvents. Among the tested catalysts, the most active, in the model hydroamination of phenylacetylene with aniline, was tested in the hydroamination of phenylacetylene with a large variety of amines. Relying on previous mechanistic studies,3 DFT (Density Functional Theory) studies were conducted to rationalized the dramatical yield difference observed by varying the activating/deactivating magnitude of the aryl substituents

Catalytic Alkylation of 2-Aryl-2-oxazoline-4-carboxylic Acid Esters Using Cyclopeptoids; Newly Designed Phase-Transfer Catalysts

Nonionic, chiral macrocyclic peptoids are efficient phase-transfer catalysts in the C-4 enantioselective alkylation of 2-[4-(trifluoromethyl)phenyl]-2-oxazoline-4-carboxylic acid esters. Screening of the structural features of cyclic peptoids, namely the ring size, symmetry elements, number of proline residues, and substituents on the side chains, showed that the alternated N-(4-methoxybenzyl)glycine/l-proline cyclohexapeptoid is the optimal catalyst (good yields and up to 75% ee) for the stereocontrolled construction of α-alkylated serine tert-butyl esters