As an important research tool, peptide have received prominence in molecular biology, clinical research, instrumentation, study of protein structure and functioning, smart biomaterials etc. This has encouraged to develop synthetic peptides (by replacing enzyme sensitive amide linkage) i.e. Peptidomimetics having enhanced stability and attractive properties. 1,2,3-triazole motif is widely accepted isosteric group to surrogate such linkages present in biopolymers. Instead of using classical approach to peptide synthesis leading to poor yield, bad control over the stereo-and regioselectivity, solubility issues, slow reaction rate, use of toxic catalysts, difficult purification etc., we have used Topochemical Azide-Alkyne Cycloaddition (TAAC, lattice controlled) reaction. Utilizing the principle of crystal engineering, we have synthesized a structurally modified dipeptide (using alanine and valine) which undergoes heat induced topochemical 1,3-dipolar cycloaddition reaction to give triazole-linked pseudopolypeptide. Also, the crystals underwent cracking due to the packing strain generated at higher temperature due to thermal topochemical polymerization. Systematic characterization is carried out to study the following TAAC reaction. [1] Biradha, K. et al. (2013) Chem. Rev. 42, 950-967.
Big defensins are two-domain antimicrobial peptides (AMPs) that have highly diversified in mollusks. Cg-BigDefs are expressed by immune cells in the oyster Crassostrea gigas, and their expression is dampened during the Pacific Oyster Mortality Syndrome (POMS), which evolves toward fatal bacteremia. We evaluated whether Cg-BigDefs contribute to the control of oyster-associated microbial communities. Two Cg-BigDefs that are representative of molecular diversity within the peptide family, namely Cg-BigDef1 and Cg-BigDef5, were characterized by gene cloning and synthesized by solid-phase peptide synthesis and native chemical ligation. Synthetic peptides were tested for antibacterial activity against a collection of culturable bacteria belonging to the oyster microbiota, characterized by 16S sequencing and MALDI Biotyping. We first tested the potential of Cg-BigDefs to control the oyster microbiota by injecting synthetic Cg-BigDef1 into oyster tissues and analyzing microbiota dynamics over 24 h by 16S metabarcoding. Cg-BigDef1 induced a significant shift in oyster microbiota β-diversity after 6 h and 24 h, prompting us to investigate antimicrobial activities in vitro against members of the oyster microbiota. Both Cg-BigDef1 and Cg-BigDef5 were active at a high salt concentration (400 mM NaCl) and showed broad spectra of activity against bacteria associated with C. gigas pathologies. Antimicrobial specificity was observed for both molecules at an intra- and inter-genera level. Remarkably, antimicrobial spectra of Cg-BigDef1 and Cg-BigDef5 were complementary, and peptides acted synergistically. Overall, we found that primary sequence diversification of Cg-BigDefs has generated specificity and synergy and extended the spectrum of activity of this peptide family.
We report a bio-inspired, strain driven epimerization of trans-ketals to cis-ketals through an enolate intermediate. Swern oxidation of a hydroxyl group adjacent to a trans-ketal effects both oxidation and its epimerization to cis-ketal. This novel and general strategy allows inversion of up to three contiguous stereocenters and has been illustrated by the synthesis of several unnatural/rare isomers of carbohydrates/cyclitols from their naturally abundant isomers.
Torbeev. Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments. Tetrahedron, Elsevier, 2018, 75 (6), pp.Please cite this article as: Baral A, Asokan A, Bauer V, Kieffer B, Torbeev V, Chemical synthesis of transactivation domain (TAD) of tumor suppressor protein p53 by native chemical ligation of three peptide segments, Tetrahedron (2018), doi: https://doi.
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