Video Experimental Relacionado

Updated: Feb 19, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Inferencia de ortólogos para la minería de enzimas para la diversificación del andamio evodiamina anticancerígeno

Brooke D Kwan^1,2, Truc Kim^1,2, Hoa Ht Nguyen^1,2

¹Department of Chemistry, Irving K. Barber Faculty of Science, University of British Columbia, 3247 University Way, Kelowna, BC, Canada.

Communications chemistry

|February 17, 2026

Resumen

Los investigadores desarrollaron un nuevo método para encontrar enzimas que puedan modificar moléculas de fármacos complejas llamadas alcaloides. Este enfoque utiliza la bioinformática para descubrir nuevas formas de crear compuestos farmacéuticos diversos y potencialmente más efectivos.

Área de la Ciencia:

Biocatálisis
Química Medicinal
Bioinformática

Sus antecedentes:

La funcionalización selectiva de andamios complejos de alcaloides es crucial para el descubrimiento de fármacos, pero es químicamente desafiante.
Las monooxigenasas de citocromo P450 ofrecen una solución al permitir la funcionalización C-H estéreo y regioselectiva.

Objetivo del estudio:

Desarrollar un flujo de trabajo dirigido para el descubrimiento de nuevas enzimas (P450) capaces de modificar andamios de alcaloides.
Aprovechar la bioinformática de inferencia de ortólogos para la minería eficiente de enzimas de diversas especies de plantas.

Principales métodos:

Análisis comparativo de 15 especies de plantas productoras de alcaloides para generar una biblioteca enfocada de 15 enzimas P450.
Cribado biocatalítico de la biblioteca de P450 contra sustratos de alcaloides.
Modelado estructural y mutagénesis dirigida para comprender las interacciones enzima-sustrato.

Principales resultados:

Se identificaron cinco enzimas P450 con actividad contra andamios de alcaloides.
Se descubrieron cuatro enzimas de distintas especies de plantas que oxigenaron selectivamente el andamio anticancerígeno evodiamina en dos posiciones.
Se dilucidó el papel del volumen hidrofóbico del sitio activo en la gobernanza del posicionamiento del sustrato y la selectividad catalítica.

Conclusiones:

El descubrimiento de enzimas guiado por ortología combinado con biocatálisis permite la funcionalización selectiva de alcaloides farmacológicamente activos.
Este enfoque integrado facilita la diversificación estructural de productos naturales complejos para el desarrollo de fármacos.
Los hallazgos abren nuevas vías para la ingeniería de enzimas para la modificación dirigida de moléculas pequeñas valiosas.

Palabras clave:

bioinformática biocatálisis química medicinal descubrimiento de fármacos alcaloides enzimas P450 evodiamina modificación química diversificación estructural

Más Videos Relacionados

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

Using Human Differentially Expressed Gene Lists to Perform Downstream Pathway Enrichment Analysis and Target Prioritization

Published on: October 3, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Videos de Conceptos Relacionados

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Structure-Activity Relationships and Drug Design

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...