Wen-Chao Yang

Central China Normal University · Department of Chemistry

We intended to highlight the interesting findings that three leucine-rich repeat receptor kinases function as receptors for sulfated plant peptide hormones, which could mediate switching between plant growth and stress tolerance. Thereafter, we proposed the potential of developing chemical regulators for promoting plant growth when they are sufferi...

High-potency 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors are usually featured by time-dependent inhibition. However, the molecular mechanism underlying time-dependent inhibition by HPPD inhibitors has not been fully elucidated. Here, based on the determination of the HPPD binding mode of natural products, the π-π sandwich stacking interac...

Plant diseases caused by bacteria have become one of the serious problems that threaten human food security, which led to the remarkable reduction of agricultural yields and economic loss. Nitroreductase (NTR), as an important biomarker, is highly expressed in bacteria, and the level of NTR is closely related to the progression of pathogen infectio...

4-Hydrophenylpyruvate dioxygenase (HPPD), a key enzyme involved in tyrosine catabolism, has long been considered a promising target for herbicides and drugs. Several types of HPPD inhibitors have been developed as high-potency drugs or herbicides. Understanding the structural basis of the binding of these inhibitors with HPPD will be beneficial for...

Background: 4-Hydroxyphenylpyruvate dioxygenase (HPPD), playing a critical role in vitamin E and plastoquinone biosynthesis in plants, has been recognized as one of the most important targets for herbicide discovery for over 30 years. Structure-based rational design of HPPD inhibitors has received more and more research interest. However, a critic...

The upregulation of 4-hydroxyphenylpyruvate dioxygenase (HPPD) can protect plants from adverse abiotic stress. Therefore, studying the changes of HPPD under abiotic stress is extremely valuable. In this study, we employed a rational molecular design strategy to prepare an HPPD-responsive fluorescent probe consisting of a pyrene fluorophore, a linke...

As biological catalysts, enzymes are vital in controlling numerous metabolic reactions. The regulation of enzymes in living cells and the amount present are indicators of the metabolic status of cell, whether in normal condition or disease. The small-molecule fluorescent probes are of interest because of their high sensitivity and selectivity, as w...

A hydroxyphenylpyruvate dioxygenase-targeted fluorescent biosensor enables the early diagnostics of abiotic stresses in plants.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a functional protein existing in almost all aerobic organisms. In the field of agricultural chemicals, HPPD is acknowledged to be one of the crucial targets for herbicides at present due to its unique bio-function in plants. In the Auto Core Fragment in silico Screening (ACFIS) web server, a potential H...

Heptamethine cyanine dyes, typified by indocyanine green (ICG), have been extensively employed as bioimaging indicators and theranostic agents. Significant efforts have been made to develop functional heptamethine cyanine dyes with outstanding bioimaging and theranostic utilities. In this work, we rationally designed and successfully developed a no...

Bacterial infection is one of the greatest threats to public health. In vivo real-time monitoring and effective treatment of infected sites through non-invasive techniques, remain a challenge. Herein, we designed a Pt(II) metallacycle-based supramolecular photosensitizer through the host–guest interaction between a pillar[5]arene-modified metallacy...

Bacterial infection is one of the greatest threats to public health. In vivo real‐time monitoring and effective treatment of infected sites through non‐invasive techniques, remain a challenge. Herein, we designed a Pt(II) metallacycle‐based supramolecular photosensitizer through the host–guest interaction between a pillar[5]arene‐modified metallacy...

Pesticide residues, significantly hampering the overall environmental and human health, have become an increasingly severe issue. Thus, developing rapid, cost-effective, and sensitive tools for monitoring the pesticide residues in food and water is extremely important. Compared to the conventional and chromatographic techniques, enzyme inhibition-b...

Biomolecules are very important for biological processes in a living being, performing similar or multiple tasks in and out of cells, tissues and other organisms at a particular location. The abnormal activity of particular biomolecule usually caused serious diseases such as Alzheimer's disease, Parkinson's disease, cancers, diabetes, cardiovascula...

Simultaneous detection of multiple cytokines is facing challenges due to cytokine complex network, dynamic and transient process of secretion. Herein we designed a molecular beacon aptamer-functionalized electrochemical sensing platform for simultaneous and real-time monitoring of three significant cytokines (VEGF, IFN-γ and TNF-α). Three biotinyla...

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for both drug and pesticide discovery. As a typical Fe(II)-dependent dioxygenase, HPPD catalyzes the complicated transformation of 4-hydroxyphenylpyruvic acid (HPPA) to homogentisic acid (HGA). The binding mode of HPPA in the catalytic pocket of HPPD is a focus of research interests....

Herbicide resistance has become one of the foremost problems in crop production worldwide. New herbicides are required to manage weeds that have evolved resistance to the existing herbicides. However, relatively few herbicides with new modes of action (MOAs) have been discovered in the past two decades. Therefore, the discovery of new herbicides (i...

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been recognized as one of the most promising targets in the field of herbicide innovation considering the severity of weed resistance currently. In a persistent effort to develop effective HPPD-inhibiting herbicides, a structure-guided strategy was carried out to perform the structural o...

In the past decades, quinazoline-2,4-dione has attracted appreciable attention in the fields of medicinal and pesticide chemistry owing to its characteristic structure and multiple promising pharmacological properties. This review covers the rational design process, optimization details, and crop safety evaluation of a class of novel 4-hydroxypheny...

The cover image is based on the Research Article Fragment‐based discovery of flexible inhibitor targeting wild‐type acetohydroxyacid synthase and P197L mutant by Ren‐Yu Qu et al., https://doi.org/10.1002/ps.5739. The cover image is based on the Research Article Fragment‐based discovery of flexible inhibitor targeting wild‐type acetohydroxyacid synt...

Near‐infrared fluorescent agents generally exhibit typical push‐pull electron characteristics, and their optical behaviors are closely related to their molecular structures. Benzobisthiadiazole moiety as a classic electron acceptor has been typically used to design the Donor‐Acceptor‐Donor (D‐A‐D) type of fluorescent/photoacoustic agents with emiss...

Pt(II)-based metallacycles, as an important family of supramolecular coordination complexes (SCCs), have exhibited excellent antitumor activity at the cell level. However, the biomedical applications of Pt(II)-based metallacycles for animal studies are still hindered by their poor stability, non-targeted tumour, and lack of detectable feedback for...

Carboxylesterases (CEs) exist as multiple types of isomers in humans, and two major types are CE1 and CE2. They are widely distributed in human tissues and well known for their important roles in drug metabolism and pathology of various diseases. Thus, the detection of CEs in living systems could provide efficient proof in disease diagnostics, as w...

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been identified as one of the most significant targets in herbicide discovery for resistant weed control. In a continuing effort to discover potent novel HPPD inhibitors, we adopted a ring-expansion strategy to design a series of novel pyrazole-quinazoline-2,4-dione hybrids based on the...

There is an increasing demand for effective noninvasive diagnosis against common pulmonary diseases which are rising sharply due to the serious air pollution. Human neutrophil elastase (HNE), a typical protease highly involved in pulmonary inflammatory diseases and lung cancer, is a potential predictor for disease progression. Currently, few of HNE...

Background: The intensifying weed resistance has challenged the use of existing acetohydroxyacid synthase (AHAS)-inhibiting herbicides. Hence, there is currently an urgent requirement for the discovery of new AHAS inhibitor to effectively control AHAS herbicide-resistant weed species caused by target mutation. Results: To combat weed resistance...

Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. This enzyme has medical signi...

The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-ben...

Succinate dehydrogenase (SDH), complex II or succinate:quinone oxidoreductase (SQR) is a crucial enzyme involved in both tricarboxylic acid cycle and oxidative phosphorylation, the two primary metabolic pathways for generating ATP. Impaired function of SDH results in deleterious disorders from cancer to neurodegeneration. SDH function is tailored i...

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a promising target for drug and pesticide discovery. The unknown binding mode of substrate is still a big challenge for the understanding of enzymatic reaction mechanism and novel HPPD inhibitor design. Herein, we determined the first crystal structure of Arabidopsis thaliana HPPD ( At HPPD) in complex...

Involved in the tyrosine degradation pathway, 4-hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for treating type I tyrosinemia. To discover novel HPPD inhibitors, we proposed a hydrophobicity-oriented drug design (HODD) strategy based on the interactions between HPPD and the commercial drug NTBC. Most of the new compounds showed im...

Slow‐binding inhibitors with long residence time on the target often display superior efficacy in vivo. Rationally designing inhibitors with low off‐target rates is restricted by a limited understanding of the structural basis of slow‐binding inhibition kinetics in enzyme‐drug interactions. 4‐Hydroxyphenylpyruvate dioxygenase (HPPD) is an important...

Nowadays, pesticide residues constitute an increasing public health concern. Cholinesterases, acetylcholinesterase, and butyrylcholinesterase, are reported to be involved in detoxification processes owing to their capability of scavenging organophosphates and carbamates. Thus, these enzymes are targeted for the discovery of sensors aiming at detect...

Butyrylcholinesterase (BChE) is widely distributed in various tissues and highly implicated in several important human diseases especially Alzheimer’s disease (AD). However, the role of BChE in AD is still controversial, which may be partially attributed to the lack of direct tool for real-time and noninvasive monitoring of BChE in in vivo. Here, w...

Chymotrypsin is a proteolytic enzyme associated with numerous biological processes. Moreover, it has been reported to be significantly involved in pancreatic diseases. Thus, its rapid and sensitive detection is of great significance for early diagnosis and related drug discovery. Herein, a new strategy of molecular docking-based virtual screening (...

4-Hydroxyphenylpyruvate dioxygenase (HPPD), a target for green herbicide discovery, has recently attracted a large number of famous scientists attention owing to controlling efficacy of resistant weeds. The structures of HPPD, inhibitors binding sites, mode of action and their metabolites are summarized. The current commercial and developing pyrazo...

The development of new herbicides is receiving considerable attention to control weed biotypes resistant to current herbicides. Consequently, new enzymes are always desired as targets for herbicide discovery. 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is an enzyme engaged in photosynthetic activity and catalyzes the transformation of...

Understanding cellular processes at molecular levels in health and disease requires the knowledge of protein-protein interactions (PPIs). In line with this, identification of PPIs at genome-wide scale is highly valuable to understand how different cellular pathways are interconnected, and it eventually facilitates designing effective drugs against...

We report herein the structure-based design and application of a fluorogenic molecular probe (BChE-FP) specific to butyrylcholinesterase (BChE). This probe was rationally designed by mimicking the native substrate and optimized stepwise by manipulating the steric feature and the reactivity of the designed probe targeting the structural difference o...

We report herein a non-peptide-based small molecule probe for fluorogenic and chromogenic detection of chymotrypsin, and the primary application. This probe was rationally designed by mimicking the peptide substrate and optimized by adjusting the recognization group. The refined probe 2 exhibits good specificity toward chymotrypsin, producing about...

A series of diphenyl ether-containing pyrazole-carboxamide derivatives was designed and synthetized as new succinate ubiquinone oxidoreductase (SQR) inhibitors. This highly potent molecular scaffold was developed from a moderately activie hit 3 obtained from our previous PFVS method. The results of greenhouse tests indicated that some analogues sho...

Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein we report the discovery of novel SQR inhibitors using pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibito...

Selenocysteine (Sec), encoded as the 21st amino acid, is the predominant chemical form of selenium that is closely related to various human diseases. Thus, it is of high importance to identify novel probes for sensitive and selective recognition of Sec and Sec-containing proteins. Although a few probes were reported to detect artificially introduce...

A benzoquinolizine coumarin based fluorescent probe was developed for detecting thiophenols, demonstrating the superior fluorescence properties caused by the decay of the twisting effect of N, N-diethylamino group of coumarin. It discriminated thiophenols from various analytes including aliphatic thiols with good selectivity, and displayed ~700-fol...

The mitochondrial respiratory complex II or succinate dehydrogenase (SDH), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, is an ideal target for fungicide development. SDH inhibitors (SDHIs) displayed a broad-spectrum activity against various fungal species. Over the last two decades, great achievement...

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of t...

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is an important enzyme in the catabolism of tyrosine, catalyzing the conversion of 4-hydroxyphenyl pyruvic acid (HPPA) into homogentisic acid (HGA), belonging to the 2-his-1-carboxylate facial triad family of non-heme iron(II) enzymes. As an important enzyme in regulating the biosynthesis of...

Exploring novel 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) inhibitors is one of the most promising research directions in herbicide discovery. To discover new triketone herbicides with broad-spectrum weed control as well as the excellent crop selectivity, a series of (total 52) novel triketone-containing quinazoline-2,4-dione derivat...

4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we ha...

Compared with naturally occurring enzymes, computationally designed enzymes are usually much less efficient, with their catalytic activities being more than six orders of magnitude below the diffusion limit. Here we use a two-step computational design approach, combined with experimental work, to design a highly efficient cocaine hydrolysing enzyme...

The development of probes for specific thiophenol detection is of great importance, due to the toxicity of thiophenols and their derivatives in environment. In the present study, a novel fluorescent probe was rationally designed for detecting thiophenols via an intramolecular charge transfer mechanism. The developed probe selectively, sensitively d...

Two novel coumarin-derived fluorescent probes were designed and synthesized for the quantitative determination of biothiols, such as cysteine (Cys), glutathione (GSH) and homocysteine (Hcy). Both probes selectively and sensitively detected biothiols in vitro, and successfully sensed biothiols in vivo with low cytotoxicity, suggesting their potentia...

Human neutrophil elastase (HNE) has been identified as a potential therapeutic target for the discovery of anti-inflammatory drugs for decades. However, little progress has been made on assays measuring the activity of HNE, especially on synthetic substrates which play essential role in determination of HNE activity. Herein, a small-molecule compou...

Cocaine is one of the most addictive drugs, and there is still no FDA (Food and Drug Administration)-approved medication specific for cocaine abuse. A promising therapeutic strategy is to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. cocaine hydrolysi...

Antimycin and cyazofamid are specific inhibitors of the mitochondrial respiratory chain, and bind to the Qi site of the cytochrome bc1 complex. With the aim to understand the detailed molecular inhibition mechanism of Qi inhibitors, we performed a comparative investigation of the inhibitory kinetics of them against the porcine bc1 complex. The resu...

As widely occurring natural products, flavonoids are an important source for drug discovery, due to their structural diversity and broad-spectrum biological activity. In this work, a library of novel, thioether-substituted flavonoids with diverse heterocyclic groups was synthesized via a microwave-assisted procedure with the advantages of good yiel...

Acetylcholinesterase (AChE) is a key enzyme of the cholinergic nervous system. More than one gene encodes the synaptic AChE target. As the most potent known AChE inhibitor, the syn1-TZ2PA6 isomer was recently shown to have higher affinity as a reversible organic inhibitor of acetylcholinesterase1 (AChE1) than the anti1-TZ2PA6 isomer. Opposite selec...

Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. In this study, we conducted a structure-based design and successfully produced a series of new multi-site AChE inhibitors with a novel framework. Compound 2e, characterized by a central benzamide moiety linked to an isoquinoline at one s...

Strobilurins are one of the most important natural products with fungicidal activities and well known for their novel action mode, broad fungicidal spectrum, lower toxicity against mammalian cells, and environmentally benign characteristics. Design and syntheses of strobilurin analogues therefore have attracted great attention in the field of agroc...

It can be argued that an ideal anti-cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma. However, wild-type BChE has a low catalytic efficiency against natu...

The cytochrome bc(1) complex (complex III, cyt bc(1)) is an essential component of cellular respiration. Cyt bc(1) has three core subunits that are required for its catalytic activity: cytochrome b, cytochrome c(1), and the Rieske iron-sulfur protein (ISP). Although most fungicides inhibit this enzyme by binding to the cytochrome b subunit, resista...

A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytoch...

Alzheimer's disease (AD) is a complex neurodegenerative disorder which seriously causes the dementia in elderly people and afflicts millions of people worldwide. Drug discovery for Alzheimer's disease therapy has been a hot research area and a big challenge, in which development of acetylcholinesterase (AChE) inhibitors design was the most active a...

3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been recognized as a promising anticancer target. Thus, it is interesting to identify new inhibitors of PDK1 for anticancer drug discovery. Through a combined use of virtual screening and wet experimental activity assays, we have identified a new PDK1 inhibitor with IC(50)=~200 nM. The antica...

A novel synthetic method of N-cyanocarboxamides has been developed with advantages of mild reaction condition, simpler procedure and easy reactant-product isolation compared with the existing methods. Using this novel method, 16 new N-cyano-1H-imidazole-4-carboxamide derivatives were synthesized and their structures were characterized by spectrum a...

Cocaine is a widely abused drug without a U.S. Food and Drug Administration-approved medication. There is a recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway [i.e., cocaine hydrolysis catalyzed by butyrylcholinest...

The cytochrome bc₁ complex (EC 1.10.2.2, bc₁) is one of the most promising targets for new drugs and agricultural fungicides. Among the existing bc₁ complex inhibitors specifically binding to the Q(o) site, oxazolidinedione derivatives have attracted great attention. With the aim to understand the substituent effects of oxazolidinedione derivatives...