Choline dendrimers as generic scaffolds for the non-covalent synthesis of multivalent protein assemblies

Abstract

A modular self-assembly strategy is presented that allows the non-covalent synthesis of multivalent protein dendrimers using the strong interaction between choline-functionalized dendrimers and the choline binding protein C-LytA. Choline dendrimers displaying fusion proteins of C-LytA and the collagen binding protein CNA35 represent attractive multivalent targeting ligands for collagen imaging.

Dynamic and bio-orthogonal protein assembly along a supramolecular polymer

“…The assembly of proteins in cells and on cell membranes is essential for a diverse range of fundamental biological processes including gene transcription, signal transduction and the regulation of metabolic pathways. [1][2][3] The underlying design principles of these natural protein assemblies such as well-dened spatial organization and shape, induced proximity, and multivalency have inspired the design of synthetic scaffolds for protein assembly based on small molecules, [4][5][6][7] dendrimers, [8][9][10] and natural and synthetic polymers, [11][12][13][14][15][16][17] which exemplify many of these benecial features with applications in diagnostics and nanotechnology. Another key element of natural protein assemblies is their reversibility which serves as a self-regulatory mechanism, for example during gene transcription, cell motility and cell division.…”

Designer Peptide and Protein Dendrimers: A Cross-Sectional Analysis

“…In 2011, Merkx and co-workers reported the noncovalent synthesis of protein dendrimers by taking advantage of the strong affinity between choline binding protein C-LytA and the fifth-generation choline-functionalized PPI dendrimer g5-CHO (Figure 62a). 233 They first fused the C-LytA with the Nterminus of well-known collagen binding protein CNA35 (Figure 62) through 28 amino acid linkers to yield the fusion protein C-LytACNA35. These fusion protein molecules were bound to choline-functionalized dendrimer g5-CHO to form protein dendrimer (Figure 62b).…”

“…These fusion protein molecules were bound to choline-functionalized dendrimer g5-CHO to form protein dendrimer (Figure b). This noncovalent protein dendrimer was used as a collagen imaging probe …”

“…(a) Structure of the C-LytA dimer, CNA35, and choline dendrimer g5-CHO, (b) binding of C-LytACNA35 fusion proteins to choline dendrimers, and (c) collagen targeting of multivalent protein dendrimers. Reproduced with permission from ref . Copyright 2011 Royal Society of Chemistry.…”

Selbstorganisierte Multivalenz: dynamische Ligandenanordnungen für hochaffine Bindungen

“…Die Wahl der hydrophoben Einheit bestimmt die Oberflächenladungsdichte der erhaltenen Nanostruktur, die direkt mit der DNA-Bindungsaffinität korreliert werden kann. [42] Multivalenz Angewandte Chemie tivalenten Anordnungen. [48b] In aktuellen Studien setzten wir abbaubare Dendrone auf Esterbasis [49] ein und zeigten, dass die Liganden bei hydrolytischem Abbau in Wasser bei pH 7.4 von der hydrophoben Einheit abgetrennt werden und die Nanostruktur zerfällt, sodass sie nicht mehr an DNA binden kann.…”