Drug discovery for enzymes.

  title={Drug discovery for enzymes.},
  author={Arne Christian Rufer},
  journal={Drug discovery today},
  • A. Rufer
  • Published 14 January 2021
  • Biology, Chemistry
  • Drug discovery today

On-flow enzymatic inhibitor screening: The emerging success of liquid chromatography-based assays

This review covers articles from the last decade that combine the use of varied immobilization methods on different solid supports and several equipment setups in on-flow systems, emphasizing the performance and capacity of recognizing and identifying biologically active compounds in various matrices.

Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases

This review crisply encapsulates enzyme inhibitory activities of various grape polyphenols towards different key human-ailment-associated enzymes: xanthine oxidase (gout), tyrosinase (hyperpigmentation), α-amylase and α-glucosidase (diabetes mellitus), pancreatic lipase (obesity), cholinesterase (Alzheimer’s disease), angiotensin i-converting enzymes (hypert

A Comprehensive Guide for Assessing Covalent Inhibition in Enzymatic Assays Illustrated with Kinetic Simulations

Four stepwise protocols to assess the biochemical potency of (ir)reversible covalent enzyme inhibitors targeting a nucleophilic active site residue are included, with accompanying data analysis tailored to the covalENT binding mode.

A review on benefits of mass spectrometry for the small molecule drug discovery

The current review describes MS strategies which are used to enhance and accelerate drug identification besides degradation linked impurities in active pharmaceutical ingredients (API) or articulated products.

How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?

Arguments whereby the PCSKs could represent a powerful arsenal to limit viral infections causing the present and future pandemics are presented.

Tanacetum vulgare L. (Tansy) as an effective bioresource with promising pharmacological effects from natural arsenal.

  • Gunes AkR. Gevrenova C. Ferrante
  • Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2021

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates.

Physicochemical Insights on Terahertz Wave Diminished Side Effects of Drugs from Slow Dissociation.

Dopamine D2 receptors (D2Rs) are one of the most intensely investigated and well-established drug targets for neuropsychiatric disorders. Selective D2R antagonists have been developed as efficacious

Metabolomics-Based Pharmacodynamic Analysis of Zhuang Yao Shuang Lu Tong Nao Granules in a Rat Model of Ischemic Cerebral Infarction

This metabolomics-based study showed that YHT could be used to treat ischemic stroke by modulating changes in endogenous metabolites in rats with cerebral ischemia.

Renewable processes of synthesis of biolubricants catalyzed by lipases



Defining Balanced Conditions for Inhibitor Screening Assays That Target Bisubstrate Enzymes

A theoretical analysis is provided, on the basis of the Cheng-Prusoff derivation, of the IC50/K i relationship of bisubstrate enzyme reactions following various sequential kinetic mechanisms, as well as the application and limitations of this information for defining optimal screening conditions for such enzymes.

Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases.

This work reviews therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.

Statistical Mechanics of Allosteric Enzymes.

This work models allosteric enzymes and their interaction with two key molecular players-allosteric regulators and competitive inhibitors and applies this model to characterize existing data on enzyme activity, comment on how enzyme parameters can be experimentally tuned, and make novel predictions on how to control phenomena such as substrate inhibition.

Structural basis for ligand binding to an enzyme by a conformational selection pathway

A molecular description of a high-energy enzyme state in a conformational selection pathway is presented by an experimental strategy centered on NMR spectroscopy, protein engineering, and X-ray crystallography and it is discovered that the structural sampling of the substrate free enzyme corresponds to the complete amplitude that is associated with formation of the closed and catalytically active state.

High performance enzyme kinetics of turnover, activation and inhibition for translational drug discovery

In vivo enzyme and substrate abundance and their dynamics, binding modality, drug binding kinetics and enzyme’s position in metabolic networks should be assessed to gauge the translational impact on drug efficacy and safety and integrating these factors in a systems biology and systems pharmacology model should facilitate translational drug discovery.

Protein Allostery in Rational Drug Design.

  • T. Kinoshita
  • Biology
    Advances in experimental medicine and biology
  • 2019
This chapter focuses on protein kinases that transfer the phosphate group of ATP to the hydroxyl group of a substrate protein, and a protein kinase inhibitor bound to the allosteric region is advantageous in terms of selectivity compared to the traditional ATP-competitive one.

Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

This Review summarizes recent developments in this field, with a particular focus on the use of degraders as research tools to interrogate complex biological problems.

Targeted protein degradation and the enzymology of degraders.

Mechanism of Selective Enzyme Inhibition through Uncompetitive Regulation of an Allosteric Agonist.

It is discovered that CE3F4R binds within the EPAC cAMP-binding domain (CBD) at a subdomain interface distinct from the cAMP binding site, acting as a wedge that stabilizes a cAMP -bound mixed-intermediate.

Activity-based protein profiling: from enzyme chemistry to proteomic chemistry.

The basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application are reviewed.