Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization: Simple Access to Bioactive Backbones.

Cyclic polymers display unique physicochemical and biological properties. However, their development is often limited by their challenging preparation. In this work, we present a simple route to cyclic poly(α-peptoids) from N-alkylated-N-carboxyanhydrides (NNCA) using LiHMDS promoted ring-expansion polymerization (REP) in DMF. This new method allows the unprecedented use of lysine-like monomers in REP to design bioactive macrocycles bearing pharmaceutical potential against Clostridioides difficile, a bacterium responsible for nosocomial infections.

Synthetic Polypeptide Polymers as Simplified Analogues of Antimicrobial Peptides.

Antimicrobial peptides (AMPs) are naturally occurring macromolecules made of amino acids that are potent broad-spectrum antibiotics with potential as novel therapeutic agents. This review aims to summarize the fundamental principles concerning the structure and mechanism of action of these AMPs, in order to guide the design of polymeric analogues that organic chemistry can generate. Among those simplified analogues, this review particularly focuses on those made of amino acids called polypeptide polymers: they are showing great potential by providing one of the best biomimetic and bioactive structures for further biomaterials science applications.

Star-Like Polypeptides as Simplified Analogues of Horseradish Peroxidase (HRP) Metalloenzymes.

Peroxidases, like horseradish peroxidase (HRP), are heme metalloenzymes that are powerful biocatalysts for various oxidation reactions. By using simple grafting-from approach, ring-opening polymerization (ROP), and manganese porphyrins, star-shaped polypeptides analogues of HRP capable of catalyzing oxidation reactions with H2O2 is successfully prepared. Like their protein model, these simplified analogues show interesting Michaelis-Menten constant (KM) in the mM range for the oxidant. Interestingly, the polymer structures are more resistant to denaturation (heat, proteolysis and oxidant concentration) than HRP, opening up interesting prospects for their use in catalysis or in biosensing devices.

New 8-Nitroquinolinone Derivative Displaying Submicromolar in Vitro Activities against Both Trypanosoma brucei and cruzi.

An antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 µM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = -0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds.