A5021230932- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Cell Adhesion Molecules Research
- Carbohydrate Chemistry and Synthesis
- Click Chemistry and Applications
- Synthetic Organic Chemistry Methods
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Molecular spectroscopy and chirality
- Microbial Natural Products and Biosynthesis
- Catalytic Cross-Coupling Reactions
- Marine Sponges and Natural Products
- Signaling Pathways in Disease
- Asymmetric Synthesis and Catalysis
- Neuropeptides and Animal Physiology
- Protein Structure and Dynamics
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Biochemical and Structural Characterization
- Crystallography and molecular interactions
- Advanced NMR Techniques and Applications
National Chemical Laboratory
2016-2025
Academy of Scientific and Innovative Research
2016-2025
Center for Integrated Protein Science Munich
2012-2018
Technical University of Munich
2009-2018
Institute for Advanced Study
2012-2018
Council of Scientific and Industrial Research
2011-2016
Indian Institute of Chemical Technology
2005-2010
RMIT University
2008
Jadavpur University
2008
Insufficient oral bioavailability is considered as a key limitation for the widespread development of peptides therapeutics. While small organic compounds often estimated from simple rules, similar rules do not apply to peptides, and even high that described number well understood. Here we present two highly Caco-2 permeable template structures based on library 54 cyclo(-d-Ala-Ala5-) with different N-methylation patterns. The first (all-trans) structure possesses β-turns type II along...
Abstract Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer’s disease. Inhibition therefore potential therapeutic strategy to ameliorate Phytochemicals are being highlighted as inhibitors. Epigallocatechin-3-gallate (EGCG) an active phytochemical green tea that has shown its potency against various diseases including inhibition repeat Tau. The EGCG altering PHF assembly full-length human not been fully explored. By biophysical biochemical analyses like ThS...
Abstract The αvβ6 integrin binds the RGD‐containing peptide of foot and mouth disease virus with high selectivity. In this study, long binding helix ligand was downsized to an enzymatically stable cyclic endowed sub‐nanomolar affinity toward receptor remarkable selectivity against other integrins. Computational studies were performed disclose molecular bases underlying subtype peptide. Finally, utility for use in biomedical also demonstrated here.
Integrins are the major class of cell adhesion proteins. Their interaction with different ligands extracellular matrix is diverse. To get more insight into these interactions, artificial endowed a well-defined activity/selectivity profile necessary. Herein, we present library cyclic pentapeptides, based on our previously reported peptide motif c(-phg-isoDGR-X-), in which high activity toward fibronectin binding integrins α5β1 and αvβ6 not vitronectin αvβ3 αvβ5 has been achieved by changing...
N-heterocyclic carbene (NHC) organocatalysis is widely employed for the umpolung of aldehydes and recently to Michael acceptors aldimines. Described herein NHC-organocatalyzed aldimines enantioselective synthesis nitrogen heterocycles. The bisimines generated from condensation 1,2-phenylenediamines salicylaldehydes undergo intramolecular cyclization in presence a chiral NHC catalyst, resulting formation dihydroquinoxalines moderate good yields er values. Detailed DFT studies shed light on...
Abstract We report, for the first time, remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized leaves plant widely used in traditional medicine is rich resource several anticancer molecules. Uttroside that comprises β-D-glucopyranosyl unit at C-26 furostanol β-lycotetraosyl C-3, ten times more cytotoxic to cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib 5.8 μM), only FDA-approved drug...
Abstract Recently, oral absorption of cyclic hexapeptides was improved by N ‐methylation their backbone amides. However, the number and position ‐methylations or solvent exposed NHs did not correlate to intestinal permeability, measured in a Caco‐2 model. In this study, we investigate enantiomeric pairs three polar two lipophilic peptides demonstrate participation carrier‐mediated transporters. As expected, all exhibited identical lipophilicity (log D 7.4 ) passive transcellular permeability...
Integrins play important roles in physiological and pathophysiological processes. Among the RGD-recognizing integrin subtypes, αvβ8 receptor is emerging as an attractive target because of its involvement various illnesses, such autoimmune diseases, viral infections, cancer. However, functions have, so far, not been investigated living subjects mainly lack a selective ligand. Here, we report design potential medical applications cyclic octapeptide first highly small-molecule ligand for αvβ8....
Abstract In this study, we present graphene oxide derivatized with cyclopentylamine (GO‐d‐CP) as a DMSO‐compatible liquid crystal alignment medium that is free from any background NMR signal for application in anisotropic NMR. This novel facilitates optimal isotropic and conditions within single sample preparation, controlled by sonication, thereby enabling the measurement of parameters‐ residual dipolar couplings (RDC) chemical shift anisotropy (RCSA). GO‐d‐CP offers several advantages,...
Abstract The merger of peptide and heterocyclic chemistry presents significant opportunities for enhancing the structural functional diversity therapeutic agents. In this study, we introduce a streamlined on‐resin method to modify peptides at N ‐terminus amines side chain Lys/Orn amino acids by incorporating biologically active triazolobenzodiazepine scaffold. presented solid‐phase synthesis (SPPS), core is formed through combination ‐alkylation, amide bond formation, an alkyne‐azide...
Stretched gelatin has been known as a chiral discriminator in aqueous solution for several years, measured by differences anisotropic NMR parameters like residual dipolar couplings. The extension of the method to higher temperatures and important solvent DMSO cross-linking with accelerated electrons potentially opens field variety polar molecules (see figure).
Abstract Recent structural studies on libraries of cyclic hexapeptides led to the identification common backbone conformations that may be instrumental oral availability peptides. Furthermore, observation differential Caco‐2 permeabilities enantiomeric pairs some these peptides strongly supports concept conformational specificity driven uptake and also suggests a pivotal role carrier‐mediated pathways for peptide transport, especially scaffolds polar nature. This work presents investigations...
Abstract The RGD‐recognizing αvβ6 integrin has only recently emerged as a major target for cancer diagnosis and therapy. Thus, the development of selective, low‐molecular‐weight ligands this receptor is still in great demand. Here, metadynamics‐driven design strategy allowed us to successfully convert helical nonapeptide into cyclic pentapeptide ( 6 ) showing remarkable potency specificity. NMR docking studies elucidated reasons high affinity selectivity compound, setting ground rational new...
Histone deacetylase 6 is a class II histone primarily present in the cytoplasm and involved regulation of various cellular functions. It consists two catalytic domains unique zinc finger ubiquitin binding protein domain, which sets it apart from other HDACs. HDAC6 known to regulate activities by modifying function microtubules, HSP90, cortactin through deacetylation. Apart activity HDAC6, interacts with proteins either SE14 domain or ZnF UBP modulate their Here, we have studied role as...
A catalyst system consisting of a copper-aluminum hydrotalcite-chiral diphosphine ligand effects asymmetric hydrosilylation several ketones, using polymethylhydrosiloxane (PMHS) as the stoichiometric reducing agent at room temperature, with moderate-to-excellent enantioselectivities. The is recovered by simple centrifugation, and efficiency remains almost unaltered even after cycles.
Abstract A highly systematic approach for the development of both orally bioavailable and bioactive cyclic N‐methylated hexapeptides as high affinity ligands integrin αvβ3 is based on two concepts: a) screening systematically designed libraries with spatial diversity b) masking peptide charge a lipophilic protecting group. The key steps method are 1) initial design combinatorial library analogues stem cyclo( d ‐Ala‐Ala 5 ); 2) selection peptides highest intestinal permeability; 3)...
Enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters has been demonstrated by the N-heterocyclic carbene (NHC)-catalyzed functionalization benzylic C(sp3)–H bonds. The NHC-catalyzed reaction enals dinitrotoluene derivatives under oxidative conditions proceeds via chiral α,β-unsaturated acylazoliums and produces in good yields excellent diastereoselectivity enantioselectivity. This mild atom-economic cascade takes place a Michael/Michael/lactonization...
The first total synthesis of the proposed structure solomonamide B has been achieved. However, 1H and 13C NMR spectral data synthesized compound was not exactly matching with that natural B. This prompted us to revise originally structure, in particular, stereochemistry nonpeptide part, which confirmed by its synthesis. During course synthesis, we have developed an interesting hydroxy group directed Wacker oxidation internal olefins a macrocyclic setting.
Although NHC-catalyzed umpolung of imines are known, the related reactions under oxidative conditions limited. Described herein is two-step process involving initial formation aldimines from corresponding aldehydes and 2-amino benzyl alcohols followed by cyclization proceeding via imidoyl azoliums conditions. The reaction allowed synthesis trifluoromethylated 3,1-benzoxazines in good yields broad scope. role NHC intramolecular preliminary mechanistic experiments also provided.
An efficient protocol has been developed using d-(2R)-Oppolzer sultam as a chiral auxiliary for generating anti/syn diastereomers with high enantiopurity and utilized in the synthesis of natural product belactosin C their synthetic congeners. It observed that variation stoichiometry Lewis acid led to difference selectivity.
The oligomers of constrained cis-exo-β-norbornene amino acid were synthesised and characterised by extensive NMR, CD, IR MD studies. results showed the formation both right left handed consecutive 6-membered hydrogen-bonded strands for [2S,3R] [2R,3S] enantiomers, respectively.