Thimmaiah Govindaraju

• Ph.D
• Professor (Full) at Jawaharlal Nehru Centre for Advanced Scientific Research

Enzyme-instructed self-assembly (EISA) is a promising approach to anti-cancer therapeutics due to its precise targeting and unique cell death mechanism. In this study, we introduce a small molecule, DN6, which...

Identifying distinct noncanonical structures in pathogenic genomes is crucial for developing new diagnostic tools. This study uncovers stable G-quadruplex (GQ) structures in conserved DNA sequences unique to the monkeypox virus...

Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60–80 % of all dementia cases. Currently, there are no curative or d...

Polycatechols modulate amyloid-associated toxicities, arrest labile iron, inhibit lipid peroxidation, and regulate tau liquid–liquid phase separation (LLPS) to mitigate the pathological nexus between ferroptosis and AD.

Cytosine‐rich DNA sequences can fold into intercalated motifs known as i ‐motifs, through noncanonical hydrogen bonding interactions. Molecular probes can provide valuable insights into the conformational stability and potential cellular functions of i ‐motifs. W 5 K 5 , a decapeptide composed of alternating tryptophan (W) and lysine (K) units, has...

Molecular tools that modulate tau liquid-liquid phase separation (LLPS) promise to treat tauopathies. We screened a set of polyphenols and demonstrated concentration-dependent biphasic modulation of tau LLPS by gallic acid...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the build-up of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Ferroptosis, an iron (Fe)-dependent form of cell death plays a significant role in the multifaceted AD pathogenesis through generation of reactive oxygen species (ROS), mito...

The aggregation of amyloid proteins in the brain is a significant neurotoxic event that contributes to neurodegenerative disorders. The aggregation of amyloid beta (Aβ), particularly Aβ42 monomers, into various forms...

P38γ (MAPK12) is predominantly expressed in triple negative breast cancer cells (TNBC) and induces stem cell (CSC) expansion resulting in decreased survival of the patients due to metastasis. Abundance of G-rich sequences at MAPK12 promoter implied the functional probability to reverse tumorigenesis, though the formation of G-Quadruplex (G4) struct...

Thimmaiah Govindaraju introduces the themed collection on molecular and nanotheranostics.

Enzymes with well-defined three-dimensional structure have in-built information for molecular organization in the near vicinity of the active sites—popularly known as enzyme architecture. Over the past few years, molecular assembly has been exploited in creating artificial enzyme or catalyst architectures. Emergent spatiotemporal structure and cata...

Reactive oxygen, nitrogen and sulfur species (RONSS) collectively encompasses a variety of energetically dynamic entities that emerge as inherent characteristics of aerobic life. This broad category includes reactive oxygen species...

Efficient delivery of bioactive ingredients into cells is a major challenge. Cell-penetrating peptides (CPPs) have emerged as promising vehicles for this purpose. We have developed novel CPPs derived from the flexible and disordered tail extensions of DNA-binding Ku proteins. Ku-P4, the lead CPP identified in this study, is biocompatible and displa...

The most promising alternative for next-generation molecular computers is biocomputing, which uses DNAs as its primary building blocks to perform a Boolean operation. DNA nanoclusters (NCs) have emerged as promising candidates for biosensing applications due to their unique self-assembly properties and programmability. It has been demonstrated that...

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we...

Neuroinflammation, driven by activation of astrocytes and microglia, progressively increases with age and is associated with neurodegenerative disorders such as Alzheimer’s disease (AD). While the role of microglia and inflammatory pathways is well-known, mechanisms that control neuroinflammation are not well understood. Recent studies show that mi...

Theranostics, the integration of therapy and diagnostics into a single entity for the purpose of monitoring disease progression and treatment response. Diagnostics involves identifying specific characteristics of a disease, while therapeutics refers to the treatment of the disease based on this identification. Advancements in medicinal chemistry an...

Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) levels, align with the features of ferroptosis. While trad...

p38γ (MAPK12) is predominantly expressed in triple negative breast cancer cells (TNBC) and induces stem cell (CSC) expansion resulting in decreased survival of the patients due to metastasis. Abundance of G-rich sequences at MAPK12 promoter implied the functional probability to reverse tumorigenesis, though the formation of G4 structures at MAPK12...

Pathogenic genomes harboring noncanonical G-quadruplex (GQ) forming sequences are potential targets for diagnosis. The GQ-forming cDNA sequences of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) are identified and validated as reliable...

Alzheimer's disease (AD) is a major neurodegenerative disorder primarily characterized by the β-amyloid (Aβ42) misfolding and aggregation-associated multifaceted amyloid toxicity encompassing oxidative stress, neuronal death, and severe cognitive impairment. Modulation of Aβ42 aggregation via various structurally anisotropic macromolecular systems...

Liquid‐liquid phase separation (LLPS) is a complex physicochemical phenomenon mediated by multivalent transient weak interactions among macromolecules like polymers, proteins, and nucleic acids. It has implications in cellular physiology and disease conditions like cancer and neurodegenerative disorders. Many proteins associated with neurodegenerat...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a major contributor to dementia cases worldwide. AD is clinically characterized by learning, memory, and cognitive deficits. The accumulation of extracellular amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) of tau are the pathological hallmarks of AD and are explored...

Wound healing is a complex process requiring multiple biological pathways and chemical responses to be activated and synchronized to recover tissue integrity. In normal physiological circumstances, the epidermal barrier restoration process through new tissue formation is highly efficient. However, increased production of reactive oxygen species, at...

Boolean operations utilizing DNA as a platform for biocomputing have become a promising tool for next-generation bio-molecular computers. In the whole process of any binary data transmission, bit errors are unavoidable and commonly occur. Cascades of exclusive-OR (XOR) operations show the great potential to evaluate these errors by introducing a pa...

Synergistic modulation of multifaceted toxicity is the key to tackle multifactorial Alzheimer's disease (AD). The etiology of AD includes amyloid β (Aβ) amyloidosis, metal ion dyshomeostasis, reactive oxygen species (ROS), oxidative stress, mitochondrial damage, and neuroinflammation. We rationally designed multifunctional modulators by integrating...

The heterogeneity and complex nature of Alzheimer's disease (AD) is attributed to several genetic risk factors and molecular culprits. The slow pace and increasing failure rate of conventional drug discovery has led to the exploration of complementary strategies based on repurposing approved drugs to treat AD. Drug repurposing (DR) is a cost-effect...

A series of 2,2’-bipyridine derivatives appended with structurally unique biomolecular auxiliaries were synthesized and investigated for their ability to ameliorate multifaceted amyloid toxicity. Our results highlight the roles of metal-chelating...

Orchestration of differential architectures of designer peptidomimetics that modulate metal oxidation states to perform multiple chemical transformations remains a challenge. Cu-chelation and self-assembly properties of amyloid β (Aβ14-23) peptide were tuned by the incorporation of cyclic dipeptide (CDP) and pyrene (Py) as the assembly directing an...

The concept of nanoarchitechtonics was introduced to describe the correct manipulation of nanoscale materials in the creation of nano-devices and applications. Nanoarchitectonics has begun to spread into many fields including nanostructured materials synthesis, supramolecular assembly, nanoscale structural fabrications, materials hybridizations, ma...

Accumulation of amyloid-beta (Aβ) into amyloid plaques and hyperphosphorylated tau into neurofibrillary tangles (NFTs) are pathological hallmarks of Alzheimer’s disease (AD). There is a significant intra- and inter-individual variability in the morphology and conformation of Aβ aggregates, which may account in part for the extensive clinical and pa...

Nucleic acid-based architectures have opened up numerous opportunities for basic and applied research in the field of DNA nanotechnology. The scheme of molecular architectonics of nucleic acids exploits conventional and unconventional base pairing interactions to integrate molecular partners in constructing functional molecular architectures and de...

Self-cleaning surfaces are ubiquitously found in nature. Development of materials and products with self-cleaning property is highly desirable in order to avoid the regular hassle of cleaning employing hazardous and costly chemicals. The self-cleaning technologies are primarily developed based on the mechanism of non-wettable (superhydrophobic) or...

Nature is full of sophisticated structures and functions orchestrated through balanced noncovalent interactions driven by molecular assemblies. Fabrication of artificial mimics is inherently challenging due to the limited understanding and control of noncovalent interactions at the molecular level. The controlled engineering of subtle noncovalent i...

The fascinating molecular recognition and structural properties make DNA an ideal building block to construct predictable molecular and nanoarchitectures. The molecular assembly interactions guided the construction of predictable and programmable architectures with diverse geometries established in the field of DNA nanotechnology. Some of the conce...

Amyloid beta (Aβ) aggregation species-associated cellular stress instigates cytotoxicity and adverse cellular stiffness in neuronal cells. The study and modulation of these adverse effects demand immediate attention to tackle Alzheimer's disease (AD). We present a de novo design, synthesis and evaluation of Aβ14-23 peptidomimetics with cyclic dipep...

G-Quadruplex (GQ) nucleic acids are promising therapeutic targets in anticancer research due to their structural robustness, polymorphism, and gene-regulatory functions. Here, we presented the structure−activity relationship of carbazole-based monocyanine ligands using region-specific functionalization with benzothiazole (TCA and TCZ), lepidine (LC...

G-Quadruplex (GQ) nucleic acids are promising therapeutic targets in anticancer research due to their structural robustness, polymorphism, and gene-regulatory functions. Here, we presented the structure–activity relationship of carbazole-based monocyanine ligands using region-specific functionalization with benzothiazole (TCA and TCZ), lepidine (LC...

Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and Tau aggregates in the brain, which induces various pathological events resulting in neurodegeneration. There have been continuous efforts to develop modulators of the Aβ and Tau aggregation process to halt or modify disease progression. A few small‐molecule‐based inhi...

The ability of mitochondrial DNA (mtDNA) to form G‐quadruplex (GQ) structures suggest their role in diseases involving mitochondrial dysfunction. Detection and visualization of GQ structures specific to mitochondria using fluorescent probes aid in monitoring mtDNA dynamics and homeostasis. Herein, we report the first study of flavylium‐methine roto...

Cyclic dipeptides (CDPs) are the simplest form of cyclic peptides with a wide range of applications from therapeutics to biomaterials. CDP is a versatile molecular platform endowed with unique properties such as conformational rigidity, intermolecular interactions, structural diversification through chemical synthesis, bioavailability and biocompat...

The aggregation of tau protein is one of the hallmarks for Alzheimer's disease, resulting in neurodegeneration. The peptidomimetics strategy to prevent tau aggregation is more specific over other small molecules. In the present study, we analyzed the effect of amyloid-β-derived peptidomimetics for inhibiting heparin-induced tau aggregation in vitro...

The aberrant production, aggregation, and accumulation of parenchymal amyloid‐β (Aβ) is the pathological hallmark of multifaceted Alzheimer's disease (AD) etiology and accounts for neuronal loss, progressive memory impairment, and cognitive decline. An aptly designed small molecule (TGR63) effectively reduced amyloid burden in the brain, rescues ne...

The quest for mastering the controlled engineering of dynamic molecular assemblies is the basis of molecular architectonics. The rational use of noncovalent interactions to programme the molecular assemblies allow the construction of diverse molecular and material architectures with novel functional properties and applications. Understanding and co...

Alzheimer's disease (AD) is a major neurodegenerative disorder and the leading cause of dementia worldwide. Predominantly, misfolding and aggregation of amyloid‐β (Aβ) peptides associated with multifaceted toxicity is the neuropathological hallmark of AD pathogenesis and, thus the primary therapeutic target to ameliorate neuronal toxicity and cogni...

An effective optical method has been proposed using cysteine conjugated naphthalene diimide (CNC) bolaamphiphile functionalised etched Fiber Bragg grating (eFBG) sensor for selective and rapid detection of mercury (Hg²⁺) in drinking water. The sensor responds with a Bragg wavelength shift (ΔλB) to the thiol-Hg²⁺ coordination interaction between CNC...

Glycation of albumin proteins is considered the pathophysiological hallmark of several chronic fatal disorders, including diabetes mellitus (DM) and Alzheimer's disease (AD). The optical detection of glycated albumin is a simple and cost‐effective tool with diagnostic implications for DM and AD. Herein, we developed a cyano derivative of the benzot...

The preparation of stable excimer-like organic nanoclusters (ONCs) in extreme dilution is a challenging task. The scheme of molecular architectonics is adapted to engineer a noninteracting ground-state aggregation of a sugar-conjugated naphthalenediimide derivative. The dynamic molecular assembly with a two-dimensional macrosheet structure graduall...

Integration of diagnostic and therapeutic functions in a single platform namely theranostics has become a cornerstone for personalized medicine. Theranostics platform facilitates noninvasive detection and treatment while allowing the monitoring of disease progression and therapeutic efficacy in case of chronic conditions of cancer and Alzheimer's d...

Mitochondria are indispensable organelle for energy production and regulation of cellular metabolism. The structural and functional alterations to mitochondria instigate pathological conditions of cancer, aging-associated and neurodegenerative disorders. The normal functioning of mitochondria is maintained by quality control mechanisms involving dy...

The production and accumulation of toxic amyloid plaques is one of the hallmarks of Alzheimer’s disease (AD). Amyloid beta (Aβ) peptides undergo self-aggregation to form soluble oligomers, protofibrils and insoluble fibrils. This process is termed as amyloidogenesis and is a major contributor to the observed neuronal damage and memory impairment in...

The interplay of condensation and decondensation of DNA plays a crucial role in chromosome maintenance and gene expression. The molecular architectonics governing the chromatin condensation-decondensation cycle are worth studying, as DNA performs unique and distinct roles in each state and switches between two states without the loss of structural...

The cooperative non-covalent interactions arising from structurally integrated multiple molecules have emerged as a powerful tool for the creation of functional supramolecular structures. Herein, we constructed cyclic dipeptide (CDP)–polydiacetylene (PDA) conjugate (CDP–DA) by introducing cyclo(L-Phe-L-Lys) to the linear 10,12-pentacosadiynoic acid...

Turn-on fluorescent probes show enhanced emission upon DNA binding, advocating their importance in imaging cellular DNA. We have probed the DNA binding mode of thiazole-coumarin (TC) conjugate, a recently reported hemicyanine-based turn-on red fluorescent probe, using a number of biophysical techniques and a series of short oligonucleotides. TC exh...

Alzheimer's disease (AD) is a major neurodegenerative disorder and the leading cause of dementia worldwide. Predominantly, misfolding and aggregation of amyloid-β (Aβ) peptides associated with multifaceted toxicity is the neuropathological hallmark of AD pathogenesis and thus, primary therapeutic target to ameliorate neuronal toxicity and cognitive...

Protein misfolding and aggregation is the pathological hallmark of Alzheimer’s disease (AD). The etiopathogenesis of AD involves the accumulation of amyloid-β (Aβ) plaques in the brain, which disrupt the neuronal network and communication causing neuronal death and severe cognitive impairment. Modulation of Aβ aggregation by exogenous therapeutic a...

The selective recognition and imaging of oncogene specific G-quadruplex (GQ) structures holds great promise in the development of diagnostic therapy (theranostics) for cancer and has been challenging due to their structural dynamics and diversity. We report selective recognition of GQ by a small molecule through unique hybrid loop stacking and groo...

Self‐cleaning surface coatings is ubiquitous with variety of products today including glass and ceramic tiles, anti‐fogging mirrors, paints, mortars, and concrete. The phenomenon of self‐cleaning is attributed to superhydrophobic surface capable of cleaning itself without any human intervention. The development of superhydrophobic surfaces has been...

Diabetes is a chronic disease affecting over 400 million people worldwide. Inadequate production of insulin due to loss of beta cells or insulin resistance within the body imbalances the glucose homeostasis, result in abrupt increase of blood glucose level. The conventional and last resort of treatment involves repeated subcutaneous insulin injecti...

Get in early: Post‐translational modifications (PTMs) of various proteins play crucial role in the pathophysiology of Alzheimer's disease (AD). Many of these aberrant PTMs are evident well before the clinical manifestation of disease and are prospective diagnostic and therapeutic targets. Global analysis of PTMs’ signature shown by the zoomed look...

Assembly and co-assemblies of peptide amphiphiles through specific noncovalent forces expand the space of molecular architectonics-driven construction of diverse nanoarchitectures with potential biological applications. In this work, cyclic dipeptide amphiphiles (CDPAs) of cyclo(Gly-Asp) with varying lengths of alkyl chains (C8-C18) were synthesize...

Lewis acidity plays a key role in the catalytic activity of lead ion (PbII) in the hydrolysis of glucose in solution under harsh synthetic conditions. We report a number of structurally similar D−gluconamide amphiphiles as functional organic ligands with active −NH center capable of coordinating PbII (viz., PbII−N−C) in basic condition to enhance t...

Multiple lines of evidence indicate that amyloid beta (Aβ) peptide is responsible for the pathological devastation caused in Alzheimer’s disease (AD). Aβ aggregation species predominantly contribute to multifaceted toxicity observed in neuronal cells including generation of reactive oxygen species (ROS), mitochondrial dysfunction, interfering with...

The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic...

The advancements in the field of imaging and diagnostics have been benefitted by the concurrent expansion of molecular probes space to monitor the diverse biological targets and events. The misfolding and aggregation of amyloid β peptide as well as Tau protein generate toxic polymorphic species (referred to as alloforms in this article) which are f...

DNA is the key biomolecule central to almost all processes in living organisms. The eccentric idea of utilizing DNA as a material building block in molecular and structural engineering led to the creation of numerous molecular-assembly systems and materials at the nanoscale. The molecular structure of DNA is believed to have evolved over billions o...

The development of novel aggregation induced emission-based fluorophoric systems (AIEgens) have gained prominent importance in recent years owing to their wide range of applications. Herein, we demonstrate the design, syntheses and molecular architectonics of cyclic dipeptides (CDPs) tethered naphthalimides (NIs) to evaluate their AIEgenic properti...

Alzheimer’s disease (AD) is one of the most prevalent forms of dementia. The current diagnosis methods based on the behavior and cognitive decline or imaging of core biomarkers viz., amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain offer poor to moderate success. Detection and imaging of biomarkers that cause additional traits...

Human civilization has witnessed the use of materials-derived from biomolecules of plants and animal origin for biomedical applications since ancient era. In recent years, precision design principles have been adopted to develop novel biomaterials derived from biomolecules. The biomolecules-derived biomaterials fabrication is dependent on chemical,...

Molecular architectonics has its essence in custom design and engineering of molecular assemblies by judicious exploitation of the noncovalent forces to construct ordered architectures with novel properties and functions. The art of mastering the programmed molecular assemblies is a challenging task owing to complex factors that govern recognition...

Alzheimer’s disease (AD) is one of the most devastating forms of dementia, without reliable treatments to cure, delay the onset of or prevent the disease progression. The proposed toxic mechanisms of AD include am-yloidogenesis of amyloid β (Aβ), metal ions dyshomeostasis, redox active metal-Aβ inclusion complex for-mation and generation of excessi...

Advances in supramolecular self-assembly have promoted the development of theranostics, the combination of both therapeutic and diagnostic functions in a single nanoplatform, which is closely associated with antitumor applications and has shown promising potential in personalized medicine. Peptide-modulated self-assembly serves as a versatile strat...

Plasmodium falciparum (Pf) 4-nitrophenylphosphatase has previously been shown to be involved in vitamin B1 metabolism. Here, conducting a BLASTP search, we found that 4-nitrophenylphosphatase from Pf has significant homology with phosphoglycolate phosphatase (PGP) from mouse, human, and yeast, prompting us to reinvestigate the biochemical propertie...

The process of protein misfolding and aggregation to form neurotoxic species is strongly implicated in most of the neurodegenerative disorders. In particular, amyloid beta (Aβ) misfolding and aggregation is central to pathophysiological processes of Alzheimer’s disease. Development of aggregation modulators has enormous implications in the discover...

The increased understanding of molecular aspects associated with chronic diseases, such as cancer and the role of tumor microenvironment, has led to the identification of endogenous and exogenous stimuli that can be exploited to devise “stimuli-responsive” materials for site-specific drug delivery applications. This book provides a comprehensive ac...

The diverse pathological mechanisms and their implications for the development of effective diagnostic and therapeutic interventions in Alzheimer's disease are presented with current progress, challenges and future prospects.