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Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Complexation Equilibria: Factors Influencing Stability of Complexes01:09

Complexation Equilibria: Factors Influencing Stability of Complexes

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In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
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Formation of Complex Ions03:45

Formation of Complex Ions

25.5K
A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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Complexation Equilibria: Overview01:23

Complexation Equilibria: Overview

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Complexation reactions take place when dative or coordinate covalent bonds form between metal ions and ligands. The compounds formed in these reactions are called coordination compounds. The number of bonds formed between the metal ion and the ligands is called its coordination number. Generally, most metal ions in an aqueous solution are solvated by water molecules and thus exist as aqua complexes.
The equilibrium constant of the complexation reaction is represented as the formation constant...
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Complexometric Titration: Ligands00:43

Complexometric Titration: Ligands

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Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...
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Video Experimental Relacionado

Updated: Jan 7, 2026

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

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Complejo de interacciones dependientes de la conformación para un PROTAC SMARCA2 y ciclodextrina

Matthew N O'Brien Laramy1, José G Napolitano1, Yuhui Zhou2

  • 1Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

Molecular pharmaceutics
|December 20, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Los degradadores de proteínas, o quimeras de targeting de proteólisis (PROTACs), exhiben propiedades conformacionales únicas que influyen en su solubilidad. Comprender estas conformaciones de PROTAC es clave para una formulación y desarrollo de fármacos eficaces.

Palabras clave:
PROTACsSMARCA2conformaciónciclodextrinadegradadores de proteínassolubilidaddegradación de proteínas dirigida

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Área de la Ciencia:

  • Bioquímica
  • Química Medicinal
  • Ciencias Farmacéuticas

Sus antecedentes:

  • Los degradadores de proteínas bivalesentes, conocidos como quimeras de targeting de proteólisis (PROTACs), representan un enfoque terapéutico novedoso.
  • Los PROTACs poseen características fisicoquímicas y estructurales únicas que pueden dificultar las propiedades biofarmacéuticas como la solubilidad, complicando el desarrollo de fármacos.
  • Existe una investigación limitada sobre estrategias de formulación específicamente diseñadas para PROTACs para abordar estos desafíos.

Objetivo del estudio:

  • Investigar los mecanismos de solubilización de un PROTAC basado en VHL (A515) dirigido a SMARCA2.
  • Elucidar el papel de la conformación molecular y la estereoquímica en la solubilidad y formulación de PROTAC.

Principales métodos:

  • Se utilizaron técnicas de espectroscopía de Resonancia Magnética Nuclear (RMN).
  • Se empleó calorimetría de titulación isotérmica (ITC).
  • Se realizaron mediciones cuantitativas de solubilidad.

Principales resultados:

  • A515 existe en dos poblaciones conformacionales distintas en solución acuosa, que difieren en la rotación del grupo amida (isómeros de prolina trans y prolina cis).
  • El isómero de prolina trans adopta conformaciones abiertas con un tamaño hidrodinámico mayor, mientras que el isómero de prolina cis forma conformaciones condensadas con un tamaño hidrodinámico menor.
  • La eficiencia de solubilización de la 2-hidroxipropil-β-ciclodextrina (HP-β-CD) varía entre estas poblaciones, influenciada por la accesibilidad de las regiones terminales de A515.

Conclusiones:

  • La conformación y la estereoquímica juegan un papel crítico, previamente no reportado, en el diseño racional de formulaciones de PROTACs.
  • Las poblaciones conformacionales distintas de los PROTACs exhiben respuestas diferenciales a excipientes solubilizantes como HP-β-CD.
  • Estos hallazgos proporcionan consideraciones específicas para la formulación de PROTACs basados en VHL para mejorar la solubilidad.