Design, Synthesis and Applications of Foldamers With Non-Coded Amino Acids

Debnath, Mintu (2018) Design, Synthesis and Applications of Foldamers With Non-Coded Amino Acids. PhD thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

This thesis entitled “Design, synthesis & applications of foldamers with non-coded amino acids” represents the synthesis, characterizations, conformational analyses, selfassociations and applications of designed peptides using coded and non-coded amino acids. The main aims of this thesis are (1) design and synthesis of non-coded amino acids, (2) to study the self-assembly of foldamers containing non-coded amino acids into different supramolecualr architecture, (3) to design peptide mimetic and study their structural heterogeneity and (4) exploring the material properties of the foldamers containing non-coded amino acids. The thesis describes the solid state conformations of hybrid helices from α-peptides composed of alternating L-Leu and Aib residues. The results suggest that the C-terminal - Aib-L-Leu-OMe segment shows an intrinsic tendency to adopt a Schellman motif induced by a distinct left-handed set of backbone torsion angles adopted by the penultimate Aib residue. The synthesis, structure and self-assembly of a designer ε-amino acid ester have been reported. FE-SEM images show that the thiocoumarin based ε-amino ester forms egg shell like nanovesicles. Further, these egg shells like nanovesicles were loaded with the antibiotic sulfamethoxazole. The growth inhibition of E. Coli as well as the spectroscopic studies show that the ε-amino ester-sulfamethoxazole formulation leads to pH responsive sustained release of the encapsulated drug. It also describes the design and synthesis of a pentapeptide containing L-phenylalanine and a central a-aminoisobutyric acid (Aib). The peptide forms a rigid 3₁₀structure with π rich channel. These π rich channels have been used as potential platform for the organic reactions. The halogenations of aniline take place without any halogen carrier (Lewis acid) and the Diels-Alder reaction between furan and maleic anhydride increases two fold in presence of the supramolecular nanoreactor. We have also reported the introduction of 3-(3-Nitro-phenyl)-acrylic acid in N-terminus of peptide and provides a new series of nitro-peptides with unsaturated backbone. The selfassembly of the foldamers were studied by single crystal X-ray diffraction analyses, solid state FT-IR spectroscopy, UV/Vis spectroscopy, fluorescence spectroscopy, FE-SEM experiments etc and characterized by NMR. We have also studied the effect of incorporation of chiral L-phenylalanine or D-phenylalanine on the supramolecular chirality of foldamers. Finally the design, synthesis and structure of a tetrapeptide containing 3-aminocinnamic acid and 2-aminoisobutyric acid have been reported. Interestingly the peptide does not form any organogel in any solvent, but on hydrogenation, the tetrapeptide provides a saturated peptide which forms instant gel in most of the aromatic solvents like xylene, toluene, 1,2-dichlorobenzene etc. The gel has been used efficiently for removal of cationic organic pollutants from waste water.

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