Auto-assemblage de pseudopeptides- Formulation d'hydrogels

• Cyclohexamer [-(D-Phe-azaPhe-Ala)2-]: good candidate to formulate supramolecular organogels.

Molecular self-assembly is a fascinating process which has become an area of great interest in supramolecular chemistry, as it leads in certain cases to molecular gels.  Molecular self-assembly is a fascinating process which has become an area of great interest in supramolecular chemistry, as it leads in certain cases to molecular gels. Organogels formulated from low molecular weight compounds (LMWOGs) have attracted much interest in the past decades due to their applications as new soft materials. Herein, we report on the ability of the cyclic pseudopeptide cyclo-[-(d-Phe-azaPhe-Ala)2-] (2) to self-assemble in some aromatic solvents and to form organogels driven by non-covalent forces, mainly hydrogen bonding and π-stacking interactions. Comprehensive FTIR and NMR studies emphasized that this cyclic aza-peptide adopts a β-turn conformation at low concentration in toluene, while an equilibrium between the monomeric states (intramolecular forces) and the supramolecular structures (intra- and intermolecular forces) is established at high concentration (gel state). Rheological investigations of the organogels highlight the dependence of their stiffness (up to ∼4 kPa) and sol/gel transition temperatures (up to 100 °C) as a function of the solvent and concentration of gelator used. The formulation of fibrous structures confirmed the phenomenon of self-assembly. Finally, we found that cyclo-[-(d-Phe-azaPhe-Ala)2-] is an effective organogelator for application in phase selective gelation (PSG) of organic solvents from aqueous/organic mixtures with recovery percents up to 96%.

DOI : 10.1039/D0RA07775E

• Improving and fine-tuning the properties of peptide-based hydrogels via incorporation of peptide nucleic acids.

Incorporation of peptide nucleic acids into peptide sequences provides new opportunities to improve and fine-tune peptide self-assembly properties. Peptide self-assemblies have attracted intense research interest over the last few decades thanks to their implications in key biological processes ( e.g., amyloid formation) and their use in biotechnological and (bio)material fields. In particular, peptide-based hydrogels have been highly considered as high potential supramolecular materials in the biomedical domain and open new horizons in terms of applications. To further understand their self-assembly mechanisms and to optimize their properties, several strategies have been proposed with the modification of the constituting amino acid chains via , per se, the introduction of d-amino acids, halogenated amino acids, pseudopeptide bonds, or other chemical moieties. In this context, we report herein on the incorporation of DNA-nucleobases into their peptide nucleic acid (PNA) forms to develop a new series of hybrid nucleopeptides. Thus, depending on the nature of the nucleobase ( i.e. , thymine, cytosine, adenine or guanine), the physicochemical and mechanical properties of the resulting hydrogels can be significantly improved and fine-tuned with, for instance, drastic enhancements of both the gel stiffness (up to 70-fold) and the gel resistance to external stress (up to 40-fold), and the generation of both thermo-reversible and uncommon red-edge excitation shift (REES) properties. To decipher the actual role of each PNA moiety in the self-assembly processes, the induced modifications from the molecular to the macroscopic scales are studied thanks to the multiscale approach based on a large panel of analytical techniques ( i.e. , rheology, NMR relaxometry, TEM, thioflavin T assays, FTIR, CD, fluorescence, NMR chemical shift index). Thus, such a strategy provides new opportunities to adapt and fit hydrogel properties to the intended ones and pushes back the limits of supramolecular materials.

HAL Id : hal-02996576, version 1

DOI : 10.1039/D0NR03483E

• The design of a new β-turn inducer is correlated to the discovery of new foldamers. In this paper, we report the liquid phase synthesis of 2:1 [α/aza]-oligomers using a convergent Boc strategy. The NMR, FTIR, restrained molecular dynamics and X-ray diffraction analyses show that 2:1 [α/aza]-oligomers adopt a C=O(i)···H–N(i + 2) hydrogen-bonded helical conformation.
  

  HAL Id : hal-01397006, version 1     DOI : 10.1002/ejoc.201402628ISTEX

The design of new cyclic pseudopeptides of the sequence 2:1-[α/aza]-hexamers, which contain aza-amino acid motifs, has gained much prominence to be involved in several potential applications. X-ray, FTIR, and NMR spectroscopy studies showed the ability of this series to adopt "-turn conformation in solid state, whereas in solution an equilibrium between the monomeric states (stabilized by "-turns through intramolecular hydrogen bonds), and supramolecular construction (stabilized by intermolecular hydrogen bonds and π-π stacking) predominates. Furthermore, both homo- and heterochiral 2:1- [α/aza]-cyclohexamers 3 and 4, respectively, can self-assemble into organized 3D structures with increases in concentration that favor the supramolecular construction in which the macrocyles are stacking over each other and stabilized by several non-covalent intermolecular interactions.      HAL Id : hal-01584156, version 1         DOI : 10.1002/ejoc.201700555