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Molecules (Basel, Switzerland)2017; 22(8); 1248; doi: 10.3390/molecules22081248

Rapid Mechanistic Evaluation and Parameter Estimation of Putative Inhibitors in a Single-Step Progress-Curve Analysis: The Case of Horse Butyrylcholinesterase.

Abstract: Highly efficient and rapid lead compound evaluation for estimation of inhibition parameters and type of inhibition is proposed. This is based on a single progress-curve measurement in the presence of each candidate compound, followed by the simultaneous analysis of all of these curves using the ENZO enzyme kinetics suite, which can be implemented as a web application. In the first step, all of the candidate ligands are tested as competitive inhibitors. Where the theoretical curves do not correspond to the experimental data, minimal additional measurements are added, with subsequent processing according to modified reaction mechanisms.
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Publication Date: 2017-07-26 PubMed ID: 28933751PubMed Central: PMC6152194DOI: 10.3390/molecules22081248Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article presents a fast and efficient approach for evaluating potential drug compounds and estimating their inhibition parameters based on a single progress-curve measurement. This method involves the use of an enzyme kinetics suite, ENZO, which can be easily implemented as a web application.

Method Overview

The study introduces a quick and efficient process for evaluating lead compounds. This approach is designed to estimate the inhibition parameters and the kind of inhibition. The method involves:

  • A single progress-curve measurement in the presence of each candidate compound.
  • Simultaneous analysis of all these curves using ENZO, an enzyme kinetics suite that can be used as a web application.

Process of Evaluation

In the first step of the evaluation, all the candidate ligands are tested as potential competitive inhibitors. The process includes:

  • Comparison of theoretical curves with the experimental data.
  • If theoretical and experimental data do not match, minimal additional measurements will be made.
  • Further processing according to modified reaction mechanisms if necessary.

This approach allows researchers to evaluate the efficacy and viability of potential inhibitors quickly and efficiently. The use of the ENZO enzyme kinetics suite also simplifies the process, allowing for easy implementation and use.

Study Significance

This research enhances the field of drug discovery and development. By presenting an accelerated method for lead compound evaluation and parameter estimation, it allows:

  • Faster identification and characterization of potential inhibitors, thus speeding up drug discovery processes.
  • Efficient use of resources, as less time and fewer materials are needed for testing.
  • Immediate implementation due to the user-friendly ENZO enzyme kinetics suite that can be accessed and utilized as a web application.

This study contributes significantly by introducing a method that expedites the drug development process, leading to potentially fast-track solutions for many health concerns.

Cite This Article

APA
Stojan J. (2017). Rapid Mechanistic Evaluation and Parameter Estimation of Putative Inhibitors in a Single-Step Progress-Curve Analysis: The Case of Horse Butyrylcholinesterase. Molecules, 22(8), 1248. https://doi.org/10.3390/molecules22081248

Publication

Molecules (Basel, Switzerland)
ISSN: 1420-3049
NlmUniqueID: 100964009
Country: Switzerland
Language: English
Volume: 22
Issue: 8
PII: 1248

Researcher Affiliations

Stojan, Jure
  • Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazovtrg 2, 1000 Ljubljana, Slovenia. stojan@mf.uni-lj.si.

MeSH Terms

  • Animals
  • Butyrylcholinesterase / chemistry
  • Butyrylthiocholine / chemistry
  • Cholinesterase Inhibitors / chemistry
  • Horses
  • Kinetics
  • Ligands
  • Models, Biological
  • Sodium Fluoride / chemistry

Conflict of Interest Statement

There are no conflicts of interest what so ever.

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Citations

This article has been cited 4 times.
  1. Lamba D, Pesaresi A. Kinetic Modeling of Time-Dependent Enzyme Inhibition by Pre-Steady-State Analysis of Progress Curves: The Case Study of the Anti-Alzheimer's Drug Galantamine. Int J Mol Sci 2022 May 3;23(9).
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  2. Petrič B, Goličnik M, Bavec A. The Removal of Time-Concentration Data Points from Progress Curves Improves the Determination of K(m): The Example of Paraoxonase 1. Molecules 2022 Feb 15;27(4).
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  3. Pajk S, Knez D, Košak U, Zorović M, Brazzolotto X, Coquelle N, Nachon F, Colletier JP, Živin M, Stojan J, Gobec S. Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes. J Enzyme Inhib Med Chem 2020 Dec;35(1):498-505.
    doi: 10.1080/14756366.2019.1710502pubmed: 31914836google scholar: lookup
  4. Li W, Liu Q, Li S, Zheng Y. New Sesquiterpenoids from the Fermented Broth of Termitomyces albuminosus and their Anti-Acetylcholinesterase Activity. Molecules 2019 Aug 16;24(16).
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