Video Experimental Relacionado

Updated: Apr 16, 2026

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Published on: August 1, 2018

Síntesis quimioenzimática de productos naturales de péptido tiazolílico que presentan una cicloadición formal [4 + 2]

Walter J Wever¹, Jonathan W Bogart¹, Joshua A Baccile²

¹†Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

Journal of the American Chemical Society

|March 6, 2015

Resumen

Los investigadores identificaron TclM, una enzima que cataliza el paso final en la biosíntesis del antibiótico tiocilina. Esto implica una reacción única de cicloadición [4+2] entre las deshidroalaninas, completando la vía del péptido tiazolilo.

Área de la Ciencia:

La bioquímica es la bioquímica.
Química de Productos Naturales Química de Productos Naturales
Enzimología Enzimología.

Sus antecedentes:

Las tiocilinas son antibióticos de péptido tiazolílico producidos por Bacillus cereus.
Su biosíntesis implica la modificación post-traduccional de los péptidos precursores.
El paso final de ciclización no se había caracterizado previamente.

Objetivo del estudio:

Para caracterizar enzimáticamente el paso final en la biosíntesis de la tiocilina.
Para identificar la enzima responsable de la propuesta [4+2] cicloadición.
Desarrollar un método para producir el sustrato de péptido complejo.

Principales métodos:

Síntesis quimoenzimática del péptido precursor de la tiocilina utilizando la ligadura química nativa (LNC).
Ensayos bioquímicos para probar la actividad de la enzima TclM.
Caracterización de la reacción de cicloadición [4+2] catalizada por TclM.

Principales resultados:

TclM, una sola enzima, fue identificada y demostrada para catalizar la cicloadición formal [4+2] entre dos deshidroalaninas.
Esta reacción representa el paso final en la biosíntesis de la tiocilina.
Se estableció una nueva ruta quimioenzimática al sustrato péptido complejo.

Conclusiones:

La enzima TclM es responsable de la única reacción de cicloadición en la biosíntesis de la tiocilina.
Este descubrimiento aclara un paso clave en la formación del producto natural del péptido tiazolilo.
La estrategia quimioenzimática desarrollada permite un mayor estudio de esta clase de enzimas y la producción de antibióticos.

Más Videos Relacionados

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

Videos de Conceptos Relacionados

Cycloaddition Reactions: Overview

Cycloaddition Reactions: Overview

Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.

Cycloaddition Reactions: MO Requirements for Thermal Activation

Cycloaddition Reactions: MO Requirements for Thermal Activation

Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.

Cycloaddition Reactions: MO Requirements for Photochemical Activation

Cycloaddition Reactions: MO Requirements for Photochemical Activation

Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.

Thermal and Photochemical Electrocyclic Reactions: Overview

Thermal and Photochemical Electrocyclic Reactions: Overview

Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.