A selection of bioactive polyphenols of different structural classes, such as the ellagitannins vescalagin and vescalin, the flavanoids catechin, epicatechin, epigallocatechin gallate (EGCG), and ...procyanidin B2, and the stilbenoids resveratrol and piceatannol, were chemically modified to bear a biotin unit for enabling their immobilization on streptavidin‐coated sensor chips. These sensor chips were used to evaluate in real time by surface plasmon resonance (SPR) the interactions of three different surface‐bound polyphenolic ligands per sensor chip with various protein analytes, including human DNA topoisomerase IIα, flavonoid leucoanthocyanidin dioxygenase, B‐cell lymphoma 2 apoptosis regulator protein, and bovine serum albumin. The types and levels of SPR responses unveiled major differences in the association, or lack thereof, and dissociation between a given protein analyte and different polyphenolic ligands. Thus, this multi‐analysis SPR technique is a valuable methodology to rapidly screen and qualitatively compare various polyphenol–protein interactions.
SPR sensor chips: Seven plant polyphenols of four different structural classes (ellagitannins, flavanols, proanthocyanidins, and stilbenoids) were synthesized and/or chemically modified at selected carbon centers for enabling their biotinylation and subsequent immobilization in order to examine their interactions with various proteins in real time by surface plasmon resonance (SPR) on streptavidin‐coated sensor chips. The SPR responses unveiled major differences in the modes of association and dissociation of these polyphenol–protein interactions.
Winding it up: The plant polyphenolic metabolite vescalagin fulfills all the requirements for use as an antiactin agent in cellular biological investigations. Despite its high hydrophilicity, it ...rapidly enters cells and disturbs the organization of the actin cytoskeleton in a dose‐dependent reversible manner by binding fibrillar actin and forcing the actin filaments (left) to wind themselves into ball‐like fibrillar aggregates (right).
Actin subunits assemble into actin filaments whose dynamics and three-dimensional architectures are further regulated by a variety of cellular factors to establish the functional actin cytoskeleton. ...The C-glucosidic ellagitannin vescalagin and its simpler analogue vescalin, affect both the dynamics and the ultrastructure of the actin cytoskeleton by directly binding to F-actin. Herein, we show that in vitro, the two compounds induce the formation of distinct F-actin networks characterized by different superstructures and dynamics. In living mature osteoclasts, highly specialized bone-degrading cells that constantly remodel their cytoskeleton, vescalagin and vescalin alter actin dynamics at podosomes and compromise the integrity of the podosome belt that forms the bone-degrading apparatus. Both compounds target the bone-resorbing activity at concentrations that preserve osteoclastic maturation and survival and with no detectable impact on the behaviour of bone-forming osteoblastic cells. This anti-osteoclastic activity of vescalagin and vescalin reveals the potential of targeting actin dynamics as a new therapeutic opportunity and, in this case, as a plausible approach for the local treatment of osteoporosis.
Ce travaille de thèse concerne la synthèse de dérivés de polyphénols de type flavanol, ellagitannins C-glucosidique et procyanidine, modifiés avec un espaceur comportant une biotine terminale. Cette ...biotine terminale a permis d’immobiliser ces polyphénols modifiés sur des surfaces SPR, permettant ainsi l’étude d’interactions polyphénol-protéine en temps réel. Ainsi, la topoisomerase II alpha et l'actine fibrilaire ont montré une plus grande affinité pour les polyphenols de type ellagitannins que pour ceux de type flavanol. Nous avons également pu montrer que d’autres protéines (BSA, myoglobine, actine globulaire, streptavidine, collagen type I) n’avaient pas d’interaction avec les flavanols et les ellagitannins.
This work concerns the synthesis of derivatives of polyphenols of the type flavanol, C-glucosidic ellagitannin and procyanidin, which are modified to bear a spacer ending with a biotin unit. This biotin ending unit allowed to immobilize these modified polyphenols on to SPR surfaces, which allowed the study of polyphenol-protein interactions in real time. The proteins topoisomerase II alpha and fibrilar actin showed a higher affinity for the polyphenols of the type ellagitannins than for those of the type flavanol. It was also showed that other proteins (BSA, myoglobin, globular actin, streptavidin, collagen type I) did not interact with either the flavanols or the ellagitannins
In zellbiologischen Studien genügt der pflanzliche Polyphenolmetabolit Vescalagin allen Anforderungen an einen Actinhemmer. Die Verbindung ist stark hydrophil, dringt aber trotzdem schnell in Zellen ...ein. Dort stört sie die Organisation des Actin‐Zytoskeletts reversibel und in dosisabhängiger Weise, indem sie an fibrilläres Actin (links) bindet und ein Aufrollen der Fasern in knäuelartige Aggregate erzwingt (rechts).
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