Sulfated glycopeptide nanostructures for multipotent protein activation

Abstract

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with very different polysaccharide binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signaling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than expected. These super-bioactive nanostructures may enable many therapies in the horizon involving proteins.

Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix

“…11) of the slow-release delivery system and the binding of the collagen element to factors in the extracellular matrix (ECM) (Supplementary Fig. 15), including collagen in the ECM, the fibronectin heparin complex and glycos-aminoglycans (for example, heparin and heparin sulfate) 26 . These interactions helped retain the injected complex for at least 14 days (Supplementary Fig.…”

Hierarchical self-assembly and emergent function of densely glycosylated peptide nanofibers

“…Notably, glycosylation facilitates hierarchical assembly of various natural protein-based structures, including acetylcholine receptors, flagella, and mucinous liquid crystals [20][21][22] . Peptide-based nanofibers modified with carbohydrates are finding increasing use as biomaterials for various applications, including growth factor delivery, lectin recognition, cell binding, and tissue regeneration [23][24][25][26][27][28][29][30] . Yet, the influence of glycosylation on synthetic peptide self-assembly has received only limited attention focused primarily on hydrogel formation, nanofiber morphology, and nanofiber solubility 31,32 .…”

Reversible Loading of Nanoscale Elements on a Multicomponent Supramolecular Polymer System by Using DNA Strand Displacement

“…[1][2][3][4][5][6][7][8][9] These features make supramolecular polymer materials excellent candidates for the construction of modular multicomponent systems, in which functional monomers can be introduced by simply matching the noncovalent interactions of the native and functional monomer units. [10][11][12] Engineering of functionw ithin shape-persistent, one-dimensional supramolecular polymers consisting of amphiphiles can involvet ethering [13][14][15][16][17] or embedding [18][19][20][21] of specific (bio)molecular or nanoscale components. For example, bioactive peptides [12,14,22] and drugs [16,23] have been incorporated into them through the use of various covalentc hemistries to prepare monomers that self-assemble into supramolecular polymers with am ultivalent presentation of ag iven component for applications in the biomedical area.…”