Wechselwirkung von Polyelektrolyt‐Architekturen mit Proteinen und Biosystemen

Abstract

Gegenionen, die die Ladungen von Polyelektrolyten wie DNA oder Heparin neutralisieren, können im Wasser dissoziieren und beeinflussen stark deren Wechselwirkung mit Biomolekülen, insbesondere mit Proteinen. In diesem Artikel geben wir einen Überblick über Studien zur Wechselwirkung von Proteinen mit Polyelektrolyten und den Nutzen dieses Wissens für die medizinische Forschung. Hauptantriebskraft für die Bindung von Proteinen an Polyelektrolyte ist die Freisetzung von Gegenionen: Positiv geladene Bereiche des Proteins werden hierbei zu mehrwertigen Gegenionen des Polyelektrolyten, sodass zuvor gebundene Gegenionen des Polyelektrolyten freigesetzt werden und sich zugleich die Entropie erhöht, wie wir anhand von Studien zu Wechselwirkung von Proteinen mit natürlichen und synthetischen Polyelektrolyten zeigen. Ein Schwerpunkt liegt dabei auf sulfatierten dendritischen Polyglycerinen (dPGS). Die Literatur zeigt, dass wir Fortschritte beim Verständnis der Ladungs‐Ladungs‐Wechselwirkung in biologisch relevanten Systemen machen. Die Forschung auf diesem Gebiet wird die Entwicklung synthetischer Polyelektrolyte für die Medizin voranbringen.

Polysulfates Block SARS-CoV-2 Uptake via Electrostatic Interactions

“…The solution structure of HPGS in aqueous solution can be approximated by a sphere with negative surface charges. [16] LPGS is a linear polymer that can attain multiple conformations and may span larger distances, and can hence conform to larger basic patches on the surface of proteins.…”

“…As discussed recently [14,[16][17][18], charge-charge interactions mainly act through counterion release: [19][20] patches of positive charge on the surface of proteins can become multivalent counterions of highly charged polyelectrolytes such as heparin, thus releasing a concomitant number of counterions condensed to the polyelectrolyte into the bulk phase. [16][17] On the other hand, positively charged patches could be a target for the design of viral-entry inhibitors. Considering that these positively charged residues are located in close vicinity of the ACE2 binding site of the spike protein [7], it is envisioned that inhibitors bound to the positively charged patches can interrupt ACE2 binding, leading to virus entry inhibition.…”

Dendrimers as Modulators of Brain Cells

“…Such interactions are of wide biological interest because they can modulate the cellular locations of HMGB1, thereby modulating its deleterious versus beneficial effects. Considering the ability to tailor the number of charges on the dendrimer surface, they seem to be interesting nano-tools for changing HMGB1 and similar transcription factor locations between the nucleus and cytosol [ 46 ]. Tailored polyion interactions between dendrimers and biomolecules will allow for strict control of the number and location of ions on these macromolecules or self-assembled supramolecular structures [ 46 ].…”

“…Considering the ability to tailor the number of charges on the dendrimer surface, they seem to be interesting nano-tools for changing HMGB1 and similar transcription factor locations between the nucleus and cytosol [ 46 ]. Tailored polyion interactions between dendrimers and biomolecules will allow for strict control of the number and location of ions on these macromolecules or self-assembled supramolecular structures [ 46 ]. Inspiration to study these interactions came from natural interactions, for example, between heparin sulfate and biomolecules [ 47 ].…”

Polysulfate hemmen durch elektrostatische Wechselwirkungen die SARS‐CoV‐2‐Infektion**

“…[13][14][15] The work presented here follows our hypothesis that charge-charge interactions are of central importance to inhibit the entry of SARS-CoV-2 into cells. As discussed recently [14,[16][17][18], charge-charge interactions mainly act through counterion release: [19][20] patches of positive charge on the surface of proteins can become multivalent counterions of highly charged polyelectrolytes such as heparin, thus releasing a concomitant number of counterions condensed to the polyelectrolyte into the bulk phase. [16][17] On the other hand, positively charged patches could be a target for the design of viral-entry inhibitors.…”