Site-selective post-modification of short α/γ hybrid foldamers: a powerful approach for molecular diversification towards biomedical applications.

The extensive research work in the exhilarating area of foldamers (artificial oligomers possessing well-defined conformation in solution) has shown them to be promising candidates in biomedical research and materials science. The post-modification approach is successful in peptides, proteins, and polymers to modulate their functions. To the best of our knowledge, site-selective post-modification of a foldamer affording molecules with different pendant functional groups within a molecular scaffold has not yet been reported. We demonstrate for the first time that late-stage site-selective functionalization of short hybrid oligomers is an efficient approach to afford molecules with diverse functional groups. In this article, we report the design and synthesis of hybrid peptides with repeating units of leucine (Leu) and 5-amino salicylic acid (ASA), regioselective post-modification, conformational analyses (based on solution-state NMR, circular dichroism and computational studies) and morphological studies of the peptide nanostructures. As a proof-of-concept, we demonstrate the applications of differently modified peptides as drug delivery agents, imaging probes, and anticancer agents. The novel feature of the work is that the difference in reactivity of two phenolic OH groups in short biomimetic peptides was utilized to achieve site-selective post-modification. It is challenging to apply the same approach to short α-peptides having a poor folding tendency, and their post-functionalization may considerably affect their conformation.

Cation-π and hydrophobic interaction controlled PET recognition in double mutated cutinase - identification of a novel binding subsite for better catalytic activity.

Accelerated hydrolysis of polyethylene terephthalate (PET) by enzymatic surface modification of various hydrolases, which would not degrade the building blocks of PET in order to retain the quality of recycled PET, is a promising research area. Many studies have been reported to identify mutations of different hydrolases that can improve PET degradation. Recently, the mutation of glycine and phenyl alanine with alanine in cutinase was found to improve the activity of PET degradation 6-fold. Yet, a deep insight into the overall structural basis as well as the explicit role played by the amino acid residues for PET degradation is still elusive, which is nevertheless important for comparative analyses, structure-function relations and rational optimization of the degradation process. Our molecular dynamics simulations coupled with quantum mechanical study demonstrate that mutations of anchor residue phenyl alanine to alanine at the PET binding cleft of cutinase unveiled a distal yet novel binding subsite, which alters the nature of dispersive interaction for PET recognition and binding. The phenyl alanine engages in π-π interaction with the phenyl ring of PET (-8.5 kcal mol-1), which on one side helps in PET recognition, but on the other side restricts PET to attain fully extended conformations over the entire binding cleft. The loss of π-π interaction due to mutation of phenyl alanine to alanine is not only compensated by the favourable cation-π and hydrophobic interactions from the arginine residues (-17.1 kcal mol-1) found in the newly discovered subsite, but also favours the fully extended PET conformation. This subsequently impacts the overall increased catalytic activity of mutated cutinase.

Effect of ancillary ligand on DNA and protein interaction of the two Zn (II) and Co (III) complexes: experimental and theoretical study.

In the present work we have developed one mononuclear Zn(II) complex [Zn(L)(H2O)] (Complex 1) by utilizing a tetracoordinated ligand H2L, formed by simple condensation of 2, 2 dimethyl 1,3 diamino propane and 3- ethoxy salicylaldehyde and one newly designed mononuclear Co (III) complex [Co(L)(L1)] (complex 2) by utilizing (H2L) and 3- ethoxy salicylaldehyde(HL1) as an ancillary ligand. The newly developed complex 2 have been spectroscopically characterized. An interesting phenomenon has been noticed that in presence of ancillary ligand, the solubility in buffer solution and the thermal stability of complex 2 comparatively increases than 1. To check the effect of ancillary ligand, present in complex 2 towards the DNA and HSA binding efficacy, both the complexes have been taken into consideration to inspect their binding potentiality with the macromolecules. The 'on', 'off' fluorescence changes in presence of DNA and HSA, the binding constant values, obtained from electronic spectral titration, iodide induced quenching, competitive binding assay, circular dichroism (CD) spectral titration, time resolved fluorescence experiment unambiguously assure the better binding efficacy of complex 2 with the signal of minor groove binding mode with DNA along with no significant conformational changes of the macromolecules. The strong and spontaneous binding of complex 2 with CT-DNA is further supported by the Isothermal Titration Calorimetry (ITC) study. Furthermore TDDFT calculation of DNA with and without complex 2 significantly authorize the formation of complex 2-DNA adduct during the association. Finally Molecular Docking study properly verifies the experimental findings and provides justified explanation behinds experimental findings.

Oxidative NHC Catalysis for the Generation of Imidoyl Azoliums: Synthesis of Benzoxazoles.

N-Heterocyclic carbene (NHC)-catalyzed intramolecular cyclization of aldimines generated from 2-amino phenols and aromatic aldehydes leading to the synthesis of 2-arylbenzoxazoles under mild conditions is presented. The reaction proceeds via the generation of the aza-Breslow intermediates from imines and NHC, which under oxidative conditions form the key imidoyl azoliums and a subsequent intramolecular cyclization furnishes the product. The reaction tolerates a broad range of functional groups, and the products are formed in generally good yields.