Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from Chinese herbal plant, Gastrodia elata, a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki 58 ± 6 nM), outperforms than kojic acid. The cell viability quantification assay demonstrate 50 μM T1 apparently attenuates 20% content...

Tyrosinase, which is the crucial copper-containing enzyme involved in melanin synthesis, strongly associated with hyperpigmentation disorders, cancer, and neurodegenerative disease; thus, it has attracted considerable interest fields of medicine cosmetics. The known tyrosinase inhibitors show numerous adverse side effects, there a lack safety regulations governing their use. As result, need to develop novel no toxicity long-term stability. In this study, we use molecular docking...

Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of cause hyperpigmentation neurodegenerative diseases. Thus, tyrosinase promising use in medicine cosmetics. Our previous study identified a natural product, A5, resembling the structure dipeptide WY apparently inhibiting tyrosinase. Here, we comprehensively estimated inhibitory capability 20 × dipeptides against mushroom We found that cysteine-containing...

Abstract Background The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay mass spectrometry. Regarding the development diagnostic antibody reagents, effective rapid preparation specific monoclonal antibodies inadequate. Methods In this study, a novel synthetic phage-displayed nanobody Golden Glove (SynaGG) library with glove-like cavity configuration was established...

Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The PD-1/PD-L1 checkpoint modulates interactions between tumor cells T been extensively targeted in immunotherapy. However, monoclonal antibodies known target this have considerable side effects, novel inhibitors are therefore required. Herein, peptide inhibitor disrupt was designed through structure-driven phage display engineering coupled computational modification optimization.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains rapidly emerging, thereby necessitating the urgent development new drugs. Two-component signal transduction systems (TCSs) signaling pathways involved in regulation various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors TCSs can disrupt signaling, growth, virulence, help combat drug-resistant TB. We conducted comprehensive...

Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, as such, it an essential target medicine cosmetics. Known tyrosinase inhibitors possess adverse side effects, there are no safety regulations; therefore, necessary to develop new fewer effects less toxicity. Peptides exquisitely specific their vivo targets, high potencies relatively few off-target effects. Thus, we...

Abstract Acinetobacter baumannii is a nosocomial pathogen that can be resistant to antibiotics by rapidly modulating its anti-drug mechanisms. The multidrug-resistant A. has been considered one of the most threatening pathogens our society. Biofilm formation and persistent cells within biofilm matrix are recognized as intractable problems, especially in hospital-acquired infections. Poly-β-1,6- N -acetyl-glucosamine (PNAG) important building blocks ’s biofilm. Here, we discover protein...

Antimicrobial peptides (AMPs) are potential candidates in designing new anti-infective agents. However, many AMPs show poor bactericidal activities physical salt and serum solutions. Here, we disclosed the structure-function relationships of a novel salt-resistant antimicrobial peptide, RR12, which could further explain its mode action applicability developing antibacterial

Monoacylglycerol lipase (MAGL), a serine hydrolase, converts endocannabinoid 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain plays bidirectional role controlling nueroinflammation. MAGL, involved Alzheimer's Parkinson's diseases, is promising target for treatment of neurodegenerative disorders. However, irreversible inhibitors MAGL lead desensitization CB1 receptors further impairing benefits associated with indirect stimulation. Therefore, development potent...

Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate (VISA), vancomycin-resistant pose significant obstacles in treating infections. Therefore, the critical need for novel drugs counter these resistant forms pressing. Two-component systems (TCSs), integral bacterial regulation, offer promising targets disruption. this study,...

Microbial infections of antibiotic-resistant strains cause serious diseases and have a significant impact on public health worldwide, so novel antimicrobial drugs are urgently needed. Insect venoms, rich source bioactive components containing peptides (AMPs), attractive candidates for new therapeutic agents against microbes. Recently, peptide, P1, identified from the venom Australian jumper ant Myrmecia pilosula, showed potent activities both Gram-negative Gram-positive bacteria, but its...

The characteristic features of two types short-term light adaptations the photosynthetic apparatus cyanobacterium Synechocystis sp. PCC 6803, state transition and blue-green light-induced fluorescence quenching, were compared in wild-type cytochrome b559 PsbJ mutant cells with mutations on near QC site photosystem II (PSII). All grew photoautotrophically assembled stable PSII. Thermoluminescence emission experiments showed a decrease stability S3QB(-)/S2QB(-) charge pairs A16FJ, S28Aβ, V32Fβ...

The emergence of antibiotic-resistant microbial strains has become a public health issue and there is an urgent need to develop new anti-infective molecules. Although natural antimicrobial peptides (AMPs) can exert bactericidal activities, they have not shown clinical efficacy. limitations native may be overcome with rational design synthesis. Here, we provide evidence that the activity synthetic peptide, GW-Q6, against Pseudomonas aeruginosa mediated through outer membrane protein OprI....

The COVID-19 pandemic resulting from the spread of SARS-CoV-2 spurred devastating health and economic crises around world. Neutralizing antibodies licensed vaccines were developed to combat COVID-19, but progress was slow. In addition, variants receptor-binding domain (RBD) spike protein confer resistance neutralizing antibodies, nullifying possibility human immunity. Therefore, investigations into RBD mutations that disrupt neutralization through convalescent are urgently required. this...

Alzheimer's disease (AD) is the leading cause of disabilities in old age and a rapidly growing condition elderly population. AD brings significant burden has devastating impact on public health, society global economy. Thus, developing new therapeutics to combat imperative. Human glutaminyl cyclase (hQC), which catalyzes formation neurotoxic pyroglutamate (pE)-modified β-amyloid (Aβ) peptides, linked amyloidogenic process that leads initiation AD. Hence, hQC an essential target for anti-AD...

Drosophila melanogaster crammer is a novel cathepsin inhibitor that involved in LTM (long-term memory) formation. The mechanism by which the inhibitory activity regulated remains unclear. In present paper we have shown oligomeric state of pH dependent. At neutral pH, predominantly dimeric vitro as result disulfide bond formation, and monomeric at acidic pH. Our inhibition assay shows crammer, not disulfide-bonded dimer, strong competitive L. Crammer molten globule solution, condition similar...

Cyclooxygenase (COX; EC: 1.14.99.1), the key enzyme in prostaglandin production human body, is a major pharmacological target for developing anti-inflammatory agents.

The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications. Here, we employed pharmacophore-based screening combined with biochemical assay molecular dynamics (MD) simulations to identify characterize inhibitors targeting SYK. built pharmacophore model, phar-TanI, successfully identified tanshinone (TanI (IC50 = 1.72 μM)) its analogs (TanIIA 3.2 μM), ST32da 46 ST32db 51 which apparently...

In Staphylococcus aureus, vancomycin-resistance-associated response regulator (VraR) is a part of the VraSR two-component system, which responsible for activating cell wall-stress stimulon in to an antibiotic that inhibits wall formation. Two VraR-binding sites have been identified: R1 and R2 vraSR operon control region. However, binding VraR promoter DNA enhancing downstream gene expression remains unclear. contains conserved N-terminal receiver domain (VraR

A new antibacterial drug is urgently needed. We employed a protein-DNA complex-guided pharmacophore modeling approach to screen inhibitors against the response regulator PmrA of polymyxin B-resistant Klebsiella pneumoniae (KP). The identified lead, E1 (IC50 = 10.2 μM), targeted DNA-binding domain (KD 1.7 whose conserved residues R171, R198, K203, and Y214 have been shown be hotspots for antimicrobial development. Treatment restored susceptibility KP B.

Comprehensive pharmacophore approaches explore the mode of action inhibitors targeting PhoP response regulator of<italic>Salmonella enterica</italic>.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs wild boars, posing significant economic repercussions global threats. Despite extensive research efforts, the development potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting AsfvPolX, key DNA repair enzyme, emerges as feasible strategy to disrupt viral replication control infections. In this study, comprehensive approach involving...