
Sumati BhatiaSwansea University | SWAN · Chemistry
Sumati Bhatia
PhD
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53
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Publications
Publications (53)
Mucus is a complex hydrogel acting as a defensive and protective barrier in various parts of the human body. The structure and composition of mucus play an important role in maintaining barrier properties by acting as a filter for the diffusion of biomolecules and pathogens. The rise in viral infections has underscored the importance of advancing r...
Here, we demonstrate the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides [LPG 40 Man 0.60 and LPG 40 (Manα1,2Man) 0.60 ]. A method based on label‐free microscale thermophoresis (MST) has been optimized to determine the direct binding affinity of multivalent mannosides for Escherichia coli (E. coli) strain ORN178 t...
Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglu...
In the last decades, various efforts have been made to synthesize optimal glycotripods for targeting trimeric glycoproteins like asialoglycoprotein receptor, hemagglutinin, and langerin. All these trimeric glycoproteins have sugar binding pockets which are highly selective for a particular carbohydrate ligand. Optimized glycotripods are high affini...
Photodynamic therapy (PDT) is emerging as an efficient strategy to combat multidrug-resistant (MDR) cancer. However, the short half-life and limited diffusion of reactive oxygen species (ROS) undermine the therapeutic outcomes of this therapy. To address this issue, a tumor-targeting nanoplatform was developed to precisely deliver mitochondria- and...
Herpes Simplex Virus ‐1 (HSV) with a diameter of 155 – 240 nm uses electrostatic interactions to bind with the heparan sulfate present on the cell surface to initiate infection. In this work, we aim to deter the initial contact using polysulfate‐functionalized hydrogels. The hydrogels provide a large contact surface area for viral interaction and s...
Molybdenum disulfide (MoS2) holds great promise for antibacterial applications owing to its strong photothermal performance and biocompatibility. Most of its antibacterial explorations have sought enhanced antibacterial potency through designing new hybrid inorganic materials, the relationship between its physiochemical properties and antibacterial...
The mucus layer is a hydrogel network that covers mucosal surfaces of the human body. Mucus has important protective properties that are related to its unique rheological properties, which are based on mucins being the main glycoprotein constituents. Mucin macromolecules entangle with one another and form a physical network that is instrumental for...
The recently emerging stem‐cell artificial niche engineering in induced pluripotent stem cell (iPSCs) 3D cultures has provided enormous opportunities to fully utilize the potential of these cells in biomedical applications. Although a fully chemically defined niche environment can supply cells with desirable safety for clinical use, establishing an...
Inhibition of respiratory viruses is one of the most urgent topics as underlined by different pandemics in the last two decades. This impels the development of new materials for binding and incapacitation of the viruses. In this work, we have demonstrated that an optimal deployment of influenza A virus (IAV) targeting ligand sialic acid (SA) on a f...
Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demons...
Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultival...
Self-assembly of non-ionic amphiphilic architectures into nanostructures with defined size, shape and morphology has garnered substantial momentum in the recent years due to their extensive applications in biomedicine. The manifestation of a wide range of morphologies such as micelles, vesicles, fibers, tubes, and toroids is thought to be related t...
Multivalent binding inhibitors are a promising new class of antivirals that prevent virus infections by inhibiting virus binding to cell membranes. The design of these inhibitors is challenging as many properties, for example, inhibitor size and functionalization with virus attachment factors, strongly influence the inhibition efficiency. Here, vir...
Two sugar PEG-based amphiphilic copolymers have been synthesized by Novozym®-435-catalyzed greener solvent free transesterification reaction of diastereomeric 2,6-anhydro-3,4,5-tri-O-benzyl-glucoheptitol and 2,6-anhydro-3,4,5-tri-O-benzyl-mannoheptitol with PEG-1000 diethyl ester in 80 and 76% yields, respectively. It has been observed that the con...
In this study, we demonstrate the concept of “topology‐matching design” for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle‐based inhibitor (nano‐inhibitor) that has a matched nanotopology to IAV virions and shows heteromultivalent inhibitory effects on hemagglutinin and neuraminidase. The synthes...
Flexible multivalent 3D nanosystems that can deform and adapt onto the virus surface via specific ligand–receptor multivalent interactions can efficiently block virus adhesion onto the cell. We here report on the synthesis of a 250 nm sized flexible sialylated nanogel that adapts onto the influenza A virus (IAV) surface via multivalent binding of i...
Multivalent virus binding inhibitors are a promising new class of antivirals, preventing virus infection of cells by inhibiting the first step in the viral infection cycle - binding of viruses to the cell surface. The design of multivalent virus binding inhibitors is complex as many properties, such as inhibitor size and functionalization with viru...
Multivalency is a key principle to reinforce reversible molecular interactions through the formation of multiple bonds. Influenza A virus deploys this strategy to bind strongly to cell surface receptors. We performed single molecule force spectroscopy (SMFS) to investigate the rupture force required to break individual and multiple bonds formed bet...
Influenza meets its match : Based on the principle of topology matching, a potent nanoparticle‐based inhibitor for influenza A was designed that shows heteromultivalent inhibition of the receptor‐binding viral proteins. This inhibitor is capable of neutralizing influenza A virus extracellularly and blocking its interaction with the host cell recept...
Fighting influenza : Through the combination of flexibility and multivalent binding, a sialylated nanogel is able to bind and adapt onto the influenza A virus surface. The resulting flexible nanogel efficiently blocks the virus binding onto the cell and inhibits infection at low pM concentrations.
Abstract
Flexible multivalent 3D nanosystems that...
We report a virus responsive hydrogel giving a dual response. The method utilizes the optical property of gold nanoparticles (AuNP) and the high swelling capacity of polyol-based hydrogels to form...
Linear and hyperbanched polyglycerol based mannosides and fucosyllactosides were developed as nanomolar binders of Mannose binding lectin (MBL) and DC-SIGN using label free microscale thermophoresis (MST) and surface plasmon resonance...
The influenza A virus infects target cells through multivalent interactions of its major spike proteins, hemagglutinin (HA) and neuraminidase (NA), with the cellular receptor sialic acid (SA). HA is known to mediate the attachment of the virion to the cell, whereas NA enables the release of newly formed virions by cleaving SA from the cell. Because...
The influenza A virus (IAV) interacts with sialic acid (SA) receptors on host cell membranes upon multivalent interactions of its major spike glycoproteins hemagglutinin (HA) and neuraminidase (NA). HA mediates the viral attachment to cells, while NA enables the release of newly formed virus particles by destroying SA receptors. Since both proteins...
The influenza A virus infects target cells through multivalent interactions of its major spike proteins, hemagglutinin (HA) and neuraminidase (NA), with the cellular receptor sialic acid (SA). HA is known to mediate the attachment of the virion to the cell, whereas NA enables the release of newly formed virions by cleaving SA from the cell. Because...
Cholera is a potentially fatal bacterial infection that affects a large number of people in the developing countries. It is caused by the cholera toxin (CT), an AB5 toxin secreted by Vibrio cholera. The toxin comprises of a toxic A-subunit and a pentameric B-subunit that binds to the intestinal cell surface. Several monovalent and multivalent inhib...
We describe the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31. Although the flexible tris‐based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a...
Indocyanine green (ICG) is a near-infrared dye for wide-ranging applications, but its utility for biological studies is limited due to poor aqueous stability and concentration-dependent aggregation. Aqueous polymeric micelles/micellar aggregates of amphiphilic copolymers could be used to protect indocyanine green (ICG) by encapsulation, which is us...
Inhibition of influenza A virus infection by multivalent sialic acid inhibitors preventing viral hemagglutinin binding to host cells of the respiratory tract is a promising strategy. However, optimal geometry and optimal ligand presentation on multivalent scaffolds for efficient inhibition both in vitro and in vivo application are still unclear. He...
Interfacial multivalent interactions at pathogen-cell interfaces can be competitively inhibited by multivalent scaffolds that prevent pathogen adhesion to the cells during the initial stages of infection. The lack of understanding of complex biological systems makes the design of an efficient multivalent inhibitor a toilsome task.Therefore, we have...
The coupling of peptides to polyglycerol carriers represents an important route towards the multivalent display of protein ligands. In particular, the inhibition of low affinity intracellular protein-protein interactions can be addressed by this design. We have applied this strategy to develop binding partners for FBP21, a protein which is importan...
For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral...
Dendritic polymers
have gained significant attention in the last two decades due to their size, shape, and multifunctionality. They have emerged as potential scaffolds for drug delivery applications. This chapter deals with the many recently developed applications of dendritic polymers in targeted drug delivery. The general properties of the dendri...
Pathogens adhere to the host cells during the first steps of infection through multivalent interactions which involve protein-glycan recognition. Multivalent interactions are also involved at different stages of immune response. Insights into these multivalent interactions generate a way to use suitable carbohydrate ligands that are attached to a b...
Multivalency is a widespread phenomenon in many biological systems, and inevitable for specific surface-surface interactions. The influenza virus provides a suitable system for studying multivalent interactions as it is covered by a densely packed layer of hemagglutinin (HA), which provides the virus high affinity to the host cells glycocalyx by mu...
An efficient, economical and industry-friendly methodology has been developed for the synthesis of C-13 side chain of taxol, (2R,3S)-3-benzamido-2- hydroxy-3-phenylpropanoic acid by oxidative cleavage of alkene precursor N-[(1S,2S)-2-(1′-ethoxyethoxy)-1-phenylbut-3-en-1-yl]benzamide using KMnO4-NaIO4-K2CO3 as oxidant in acetone-water in much higher...
The application of drug carriers for the delivery of drugs with higher biocompatibility, sustained release profile, and target specificity is a big challenge in ongoing research. Sugar-PEGylated polymers have attracted great attention in the last few years for biomedical applications as drug carriers. This is due to the higher biocompatibility of P...
To evaluate the potential of a novel dihydropyrimidinone, ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM), as a calcium channel blocker, endowed with the ability to inhibit platelet aggregation effectively.
In-vitro and in-vivo studies were conducted for the determination of antiplatelet activity using ade...
Sugar-PEG-based polymers were synthesized by enzymatic copolymerization of 4-C-hydroxymethyl-1,2-O-isopropylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-benzylidene-β-L-threo-pentofuranose/4-C-hydroxymethyl-1,2-O-isopropylidene-3-O-pentyl-β-L-threo-pentofuranose with PEG-600 dimethyl ester using Novozyme-435 (Candida antarctica lipase immo...
Coumarins, a well-known class of naturally occurring compounds, display a remarkable array of biochemical and pharmacological actions, some of which suggest that certain members of this group of compounds may significantly affect the function of various mammalian cellular systems. The development of coumarins as antioxidant agents has attracted muc...
Investigations on the role of intracellular Ca(2+) ion concentration in the mechanism of development of COPD in smokers and non-smokers were carried out. The intracellular Ca(2+) levels were found to be increased in human lymphocytes in patients with COPD as compared to non-smokers and smokers without COPD. The investigations reveal an association...
Regio- and enantioselective synthesis of (S)-(+)-3-arylamino-1-chloropropan-2-ols has been achieved by the epoxide ring opening of (±)-epichlorohydrin with different aromatic amines in the presence of Candida rugosa lipase. Activities of seven model (S)-(+)-3-arylamino-1-chloropropan-2-ols, out of 10 compounds synthesized, have been evaluated for t...
The two Upases, Novozyme®-435 and Lipozyme® TL IM has been used for diastereoselective acetylation of 4-C-hydroxymethyl-l,2-O4sopropylidene-3-O-alkyl-β-L-threo-pentofuranose in toluene. It has been observed that Novozyme*-435 mediates acetylation reaction of the dihydroxy compound with vinyl acetate leading to the formation of 5-O-acetyl-4-C-hydrox...
A series of 3-(N-alkyl-N-phenylamino)propan-2-ol derivatives were synthesized from epichlorohydrine in a multi-step strategy and were evaluated as Src kinase inhibitors. First, epoxy ring opening of epichlorohydrine was carried out in the presence of N-alkylanilines to yield 3-(N-alkyl-N-phenylamino)-1-chloro-propan-2-ol derivatives using Ca(OTf)2...
Peracylated 1-(2′-azido-α-L-arabino-/β-D-ribofuranosyl) thymine has been chemoenzymatically synthesized and subjected to deacylation studies in the presence of CAL-B (Candida antarctica lipase-B immobilized on polyacrylate) in acetonitrile. It is observed that CAL-B mediates highly selective deacylation of the ester function involving C-5′ hydroxyl...
A series of different analogs of 4-aryl-3,4-dihydropynmidin-2(1H)-one have been synthesized and their biocatalytic resolution has been carried out using immobilized lipase CAL-L(A) (immobilized on accurel). The systematic one-step procedure is developed for the synthesis of optically enriched ethyl 4-aryl-6-methyl-3,4-dihydropyrimidin-2-one-5-carbo...