Molecular Recognition of Basic Fibroblast Growth Factor by Polyoxometalates

Abstract

Proteinbinder: Bei drei repräsentativen Polyoxometallat(POM)‐Verbindungen, z. B. 1 aus der Wells‐Dawson‐Klasse, wurde eine Wechselwirkung mit dem basischen Fibroblastenwachstumsfaktor (bFGF, rechts) nachgewiesen, die die Konformation des Wachstumsfaktors drastisch verändert. POMs sind viel versprechende Leitstrukturen für Verbindungen, die möglicherweise neue Wege der Entwicklung von Wirkstoffen gegen bFGF‐induzierte Angiogenese eröffnen.

Transition-metal-substituted polyoxometalate derivatives as functional anti-amyloid agents for Alzheimer’s disease

“…Since the discovery of the antitumor activity of cisplatin, a number of inorganic metal compounds have been used as important therapeutic agents and diagnostic imaging probes [4][5][6][7][8][9][10][11][12][13][14][15] . Worldwide sales of inorganic drugs are rapidly increasing.…”

Polyoxometalates as Inhibitors of the Aggregation of Amyloid β Peptides Associated with Alzheimer’s Disease

“…[12] We reported previously that several classic POMs bind to the cationic pocket of basic fibroblast growth factor. [16] These observations may suggest that the cationic cluster HHQK of Ab could be the binding site for POMs. We first used competition assays to verify the putative POMbinding site on Ab.…”

“…[9,10] As important inorganic drug candidates, polyoxometalates (POMs) have shown promising antiviral and antitumor activities for more than a decade. [11][12][13][14][15][16] On the basis of cell-culture assays, in vitro enzymatic activity, and molecular-modeling studies, POMs have regained considerable attention as a result of their remarkable effect against acquired immune deficiency syndrome (AIDS), as demonstrated by Hill, Pope, and coworkers. [12,13] POMs can specifically bind to the basic fibroblast growth factor (bFGF) and induce dramatic conformational changes in the growth factor.…”

“…[12,13] POMs can specifically bind to the basic fibroblast growth factor (bFGF) and induce dramatic conformational changes in the growth factor. [16] POMs are early-transition-metal-oxygen-anion clusters with incomparable structural versatility and interesting properties. The unique feature of POMs is that nearly every molecular property that can influence the recognition and reactivity of POMs with target biological macromolecules is changeable, including polarity, redox potential, surface charge distribution, shape, and acidity.…”

“…[11d] Several research groups have reported detailed studies of the interaction between POMs and their target proteins. [12][13][14][15][16] Given that the size and fairly rigid, cagelike structure of many POMs are similar, and in some cases nearly identical, to the size and structure of the water-solubilized fullerene derivatives reported to have fairly good antiamyloid activity, [10] POMs may also be potential Ab inhibitors.…”