Analysis of the molecular interaction of mitragynine from kratom with human α 1 -acid glycoprotein: biophysical and molecular modeling investigations DOI
Khairul Azreena Bakar, Shevin Rizal Feroz

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: April 3, 2025

Mitragynine (MTG), the primary psychoactive alkaloid in Mitragyna speciosa (kratom), has garnered much attention for its therapeutic properties, which is attributed mainly to selective action on opioid receptors. Despite clinical potential, molecular framework of binding plasma proteins remains incomplete. Specifically, no studies have thoroughly examined interaction with α1-acid glycoprotein (AAG), a carrier protein circulatory system that influences drug disposition and bioavailability. Hence, this study aims explore dynamics between MTG AAG using combination spectroscopic, calorimetric, microscopic, computational methods. Based isothermal titration calorimetric fluorescence studies, an intermediate affinity MTG-AAG was determined (Ka ∼ 105 M-1). evidence microenvironmental changes around Trp residues, did not disrupt overall structural integrity AAG. Thermodynamic analysis indicated energetically favorable, enthalpy driven by hydrogen bonding van der Waals forces, negative entropy change suggesting more ordered complex formation. Docking showed embedded deeply within central cavity variant F1*S, enhancing stability, as opposed near entrance A. Molecular simulations supported stable complexation both variants, F1*S maintaining compactness while A exhibited slight unfolding upon binding. These findings clear significance potential applications kratom-derived drugs, especially those structurally related MTG.

Language: Английский

A Review on Perception of Binding Kinetics in Affinity Biosensors: Challenges and Opportunities DOI Creative Commons
Brandy Renee McCann,

Brandon Daniel Tipper,

Sepeedeh Shahbeigi

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

There are challenges associated with design and development of affinity biosensors due to the complicated multiphysics nature system. Understanding binding interaction between target molecules immobilized receptors its kinetics is a crucial step develop robust reliable biosensor technologies. Evaluation in becomes more important challenging for clinical samples complex matrix. Despite drastic advancements technologies, having practical perception has remained critical bottleneck limited fundamental understanding. This Review aims provide comprehensive discussion on concepts advances developed so far biosensors. Here, modeling approaches measurement techniques presented characterize interactions while effect fouling secondary factors will be discussed concept kinetics. investigate existing research gaps potential opportunities

Language: Английский

Citations

0
Analysis of the molecular interaction of mitragynine from kratom with human α 1 -acid glycoprotein: biophysical and molecular modeling investigations DOI
Khairul Azreena Bakar, Shevin Rizal Feroz

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: April 3, 2025

Mitragynine (MTG), the primary psychoactive alkaloid in Mitragyna speciosa (kratom), has garnered much attention for its therapeutic properties, which is attributed mainly to selective action on opioid receptors. Despite clinical potential, molecular framework of binding plasma proteins remains incomplete. Specifically, no studies have thoroughly examined interaction with α1-acid glycoprotein (AAG), a carrier protein circulatory system that influences drug disposition and bioavailability. Hence, this study aims explore dynamics between MTG AAG using combination spectroscopic, calorimetric, microscopic, computational methods. Based isothermal titration calorimetric fluorescence studies, an intermediate affinity MTG-AAG was determined (Ka ∼ 105 M-1). evidence microenvironmental changes around Trp residues, did not disrupt overall structural integrity AAG. Thermodynamic analysis indicated energetically favorable, enthalpy driven by hydrogen bonding van der Waals forces, negative entropy change suggesting more ordered complex formation. Docking showed embedded deeply within central cavity variant F1*S, enhancing stability, as opposed near entrance A. Molecular simulations supported stable complexation both variants, F1*S maintaining compactness while A exhibited slight unfolding upon binding. These findings clear significance potential applications kratom-derived drugs, especially those structurally related MTG.

Language: Английский

Citations

0