Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

898
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
898
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

7.3K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.3K
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

2.0K
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
2.0K
Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

2.7K
Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
2.7K
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism01:26

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism

4.0K
The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
4.0K
Regioselectivity of Electrophilic Additions-Peroxide Effect02:35

Regioselectivity of Electrophilic Additions-Peroxide Effect

10.2K
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
10.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Hierarchical small molecule inhibition of MYST acetyltransferases.

Nature communications·2026
Same author

An Optimized Route to the Syringolin Natural Products Enables Combinatorial Synthesis of Selective, Bioactive Inhibitors of the <i><i>Plasmodium falciparum</i></i> 20S Proteasome.

Journal of medicinal chemistry·2026
Same author

Combined Quantitative and Qualitative Statistical Analyses Improve Benzodiazepine Target Discovery in Label-free Affinity-Based Protein Profiling Data.

Journal of proteome research·2026
Same author

Development of Granzyme A Turn-ON Fluorescent Activity-Based Probes.

Chembiochem : a European journal of chemical biology·2025
Same author

Granzyme B-Targeting Quenched Activity-Based Probes for Assessing Tumor Response to Immunotherapy.

Journal of the American Chemical Society·2025
Same author

A Robust Fluorogenic Substrate for Chikungunya Virus Protease (nsP2) Activity.

bioRxiv : the preprint server for biology·2025

Related Experiment Video

Updated: Jan 13, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
05:07

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

Published on: June 23, 2019

7.0K

Structure-Guided Optimization of 4-Chloro-Pyrazolopyridine Analogs for Covalent PREP Inhibition.

Kalyani Thakur1, Ian Fucci2, Joshua Pandian1

  • 1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, United States.

Journal of Medicinal Chemistry
|January 9, 2026
PubMed
Summary
This summary is machine-generated.

Researchers designed novel covalent inhibitors targeting prolyl endopeptidase (PREP), a key enzyme in neurodegenerative diseases. These potent and selective PREP inhibitors offer new tools for biological research.

More Related Videos

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
14:11

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Published on: June 10, 2021

6.7K
Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
03:29

Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms

Published on: May 31, 2024

884

Related Experiment Videos

Last Updated: Jan 13, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
05:07

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

Published on: June 23, 2019

7.0K
Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
14:11

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Published on: June 10, 2021

6.7K
Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
03:29

Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms

Published on: May 31, 2024

884

Area of Science:

  • Biochemistry
  • Structural Biology
  • Medicinal Chemistry

Background:

  • Prolyl endopeptidase (PREP) is a serine protease implicated in neurodegenerative diseases.
  • PREP modulates protein-protein interactions, influencing various pathophysiological processes.

Purpose of the Study:

  • To design and synthesize novel covalent inhibitors of PREP.
  • To explore the structure-activity relationships of these inhibitors.
  • To provide tools for investigating PREP's biological functions.

Main Methods:

  • Structure-based drug design utilizing crystallographic data and molecular docking.
  • Synthesis of 4-chloro-pyrazolopyridine (CPzP) scaffold-based inhibitors.
  • Biochemical and cellular assays for potency and selectivity evaluation.
  • Molecular dynamics simulations to understand mechanism of inhibition.

Main Results:

  • Development of potent PREP inhibitors with nanomolar activity.
  • High selectivity observed against related serine proteases like FAP and DPP4.
  • Identification of CPzP scaffold targeting a noncatalytic active site cysteine.
  • Molecular dynamics suggested inhibition involves modulation of PREP's dynamic A-loop.

Conclusions:

  • A new class of structurally distinct covalent PREP inhibitors was successfully developed.
  • The inhibitors exhibit potent and selective activity, validated through biochemical and cellular assays.
  • These findings provide valuable chemical probes for further research into PREP's roles in disease.