Sulfated glycopeptide nanostructures for multipotent protein activation
Source abstract
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 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 signalling 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 that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Proteoglycans and glycosaminoglycans research · Glycosylation and Glycoproteins Research · Chemical Synthesis and Analysis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (54)
Show source-provided references
1. Xu, D. & Esko, J. D. Demystifying heparan sulfate-protein interactions. Annu. Rev. Biochem. 83, 129–157 (2014).10.1146/annurev-biochem-060713-035314 ↗
2. Edwards, I. J. Proteoglycans in prostate cancer. Nat. Rev. Urology 9, 196–206 (2012).10.1038/nrurol.2012.19 ↗
3. Hudak, J. E. & Bertozzi, C. R. Glycotherapy: new advances inspire a reemergence of glycans in medicine. Chem. Biol. 21, 16–37 (2014).10.1016/j.chembiol.2013.09.010 ↗
4. Bramono, D. S. et al. Bone marrow-derived heparan sulfate potentiates the osteogenic activity of bone morphogenetic protein-2 (BMP-2). Bone 50, 954–964 (2012).10.1016/j.bone.2011.12.013 ↗
5. Zhao, B. et al. Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2. J. Biol. Chem. 281, 23246–23253 (2006).10.1074/jbc.M511039200 ↗
6. Sadir, R., Imberty, A., Baleux, F. & Lortat-Jacob, H. Heparan sulfate/heparin oligosaccharides protect stromal cell-derived factor-1 (SDF-1)/CXCL12 against proteolysis induced by CD26/dipeptidyl peptidase IV. J. Biol. Chem. 279, 43854–43860 (2004).10.1074/jbc.M405392200 ↗
7. Lortat-Jacob, H., Baltzer, F. & Grimaud, J. A. Heparin decreases the blood clearance of interferon-γ and increases its activity by limiting the processing of its carboxyl-terminal sequence. J. Biol. Chem. 271, 16139–16143 (1996).10.1074/jbc.271.27.16139 ↗
8. Capila, I. & Linhardt, R. J. Heparin-protein interactions. Angew. Chem. Int. Ed. 41, 390–412 (2002).10.1002/1521-3773(20020201)41:3<390::AID-ANIE390>3.0.CO;2-B ↗
9. Perrimon, N. & Bernfield, M. Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404, 725–728 (2000).10.1038/35008000 ↗
10. Li, Y. C. et al. Interactions that influence the binding of synthetic heparan sulfate based disaccharides to fibroblast growth factor-2. ACS Chem. Biol. 9, 1712–1717 (2014).10.1021/cb500298q ↗
11. Ornitz, D. M. & Leder, P. Ligand specificity and heparin dependence of fibroblast growth factor receptors 1 and 3. J. Biol. Chem. 267, 16305–16311 (1992).10.1016/S0021-9258(18)42001-7 ↗
12. Murali, S. et al. Affinity-selected heparan sulfate for bone repair. Biomaterials 34, 5594–5605 (2013).10.1016/j.biomaterials.2013.04.017 ↗
13. Lever, R. & Page, C. P. Novel drug development opportunities for heparin. Nat. Rev. Drug Discov. 1, 140–148 (2002).10.1038/nrd724 ↗
14. Baskaran, S., Grande, D., Sun, X.-L., Yayon, A. & Chaikof, E. L. Glycosaminoglycan-mimetic biomaterials. 3. Glycopolymers prepared from alkene-derivatized mono- and disaccharide-based glycomonomers. Bioconjug. Chem. 13, 1309–1313 (2002).10.1021/bc0255485 ↗
15. Huang, M. L., Smith, R. A., Trieger, G. W. & Godula, K. Glycocalyx remodeling with proteoglycan mimetics promotes neural specification in embryonic stem cells. J. Am. Chem. Soc. 136, 10565–10568 (2014).10.1021/ja505012a ↗
16. Tyler, P. C., Guimond, S. E., Turnbull, J. E. & Zubkova, O. V. Single-entity heparan sulfate glycomimetic clusters for therapeutic applications. Angew. Chem. Int. Ed. 54, 2718–2723 (2015).10.1002/anie.201410251 ↗
17. de Paz, J. L., Noti, C., Bohm, F., Werner, S. & Seeberger, P. H. Potentiation of fibroblast growth factor activity by synthetic heparin oligosaccharide glycodendrimers. Chem. Biol. 14, 879–887 (2007).10.1016/j.chembiol.2007.07.007 ↗
18. Hartgerink, J. D., Beniash, E. & Stupp, S. I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).10.1126/science.1063187 ↗
19. Webber, M. J., Appel, E. A., Meijer, E. W. & Langer, R. Supramolecular biomaterials. Nat. Mater. 15, 13–26 (2015).10.1038/nmat4474 ↗
20. Kiyonaka, S. et al. Semi-wet peptide/protein array using supramolecular hydrogel. Nat. Mater. 3, 58–64 (2004).10.1038/nmat1034 ↗
21. Müller, M. K. & Brunsveld, L. A supramolecular polymer as a self-assembling polyvalent scaffold. Angew. Chem. Int. Ed. 48, 2921–2924 (2009).10.1002/anie.200900143 ↗
22. Ustun Yaylaci, S. et al. Supramolecular GAG-like self-assembled glycopeptide nanofibers induce chondrogenesis and cartilage regeneration. Biomacromolecules 17, 679–689 (2016).10.1021/acs.biomac.5b01669 ↗
23. Chabre, Y. M. & Roy, R. Multivalent glycoconjugate syntheses and applications using aromatic scaffolds. Chem. Soc. Rev. 42, 4657–4708 (2013).10.1039/c3cs35483k ↗
24. Rostovtsev, V. V., Green, L. G., Fokin, V. V. & Sharpless, K. B. A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. 41, 2596–2599 (2002).
25. Barceloux, D. G. Copper. J. Toxicol. Clin. Toxicol. 37, 217–230 (1999).10.1081/CLT-100102421 ↗
26. Cui, H. et al. Spontaneous and X-ray-triggered crystallization at long range in self-assembling filament networks. Science 327, 555–559 (2010).10.1126/science.1182340 ↗
27. Ortony, J. H. et al. Internal dynamics of a supramolecular nanofibre. Nat. Mater. 13, 812–816 (2014).10.1038/nmat3979 ↗
28. Newcomb, C. J. et al. Cell death versus cell survival instructed by supramolecular cohesion of nanostructures. Nat. Commun. 5, 3321 (2014).10.1038/ncomms4321 ↗
29. Paine-Saunders, S., Viviano, B. L., Economides, A. N. & Saunders, S. Heparan sulfate proteoglycans retain Noggin at the cell surface—a potential mechanism for shaping bone morphogenetic protein gradients. J. Biol. Chem. 277, 2089–2096 (2002).10.1074/jbc.M109151200 ↗
30. Silva, G. A. et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 303, 1352–1355 (2004).10.1126/science.1093783 ↗
31. Tantakitti, F. et al. Energy landscapes and functions of supramolecular systems. Nat. Mater. 15, 469–476 (2016).10.1038/nmat4538 ↗
32. Katagiri, T. et al. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J. Cell Biol. 127, 1755–1766 (1994).10.1083/jcb.127.6.1755 ↗
33. Lee, S. S. et al. Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis. Adv. Healthc. Mater. 4, 131–141 (2015).10.1002/adhm.201400129 ↗
34. Van Teeffelen, J. W., Brands, J., Stroes, E. S. & & Vink, H. Endothelial glycocalyx: sweet shield of blood vessels. Trends Cardiovasc. Med. 17, 101–105 (2007).10.1016/j.tcm.2007.02.002 ↗
35. Fyrner, T. et al. Saccharide-functionalized alkanethiols for fouling-resistant self-assembled monolayers: synthesis, monolayer properties, and antifouling behavior. Langmuir 27, 15034–15047 (2011).10.1021/la202774e ↗
36. Bearinger, J. P. et al. Chemisorbed poly(propylene sulphide)-based copolymers resist biomolecular interactions. Nat. Mater. 2, 259–264 (2003).10.1038/nmat851 ↗
37. Ham, H. O., Park, S. H., Kurutz, J. W., Szleifer, I. G. & Messersmith, P. B. Antifouling glycocalyx-mimetic peptoids. J. Am. Chem. Soc. 135, 13015–13022 (2013).10.1021/ja404681x ↗
38. Gandhi, N. S. & Mancera, R. L. The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug Des. 72, 455–482 (2008).10.1111/j.1747-0285.2008.00741.x ↗
39. Ruppert, R., Hoffmann, E. & Sebald, W. Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. Eur. J. Biochem. 237, 295–302 (1996).10.1111/j.1432-1033.1996.0295n.x ↗
40. Kuo, W. J., Digman, M. A. & Lander, A. D. Heparan sulfate acts as a bone morphogenetic protein coreceptor by facilitating ligand-induced receptor hetero-oligomerization. Mol. Biol. Cell 21, 4028–4041 (2010).10.1091/mbc.e10-04-0348 ↗
41. Groppe, J. et al. Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature 420, 636–642 (2002).10.1038/nature01245 ↗
42. Bhandari, M. et al. The effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb. Haemost. 80, 413–417 (1998).10.1055/s-0037-1615222 ↗
43. Yu, P. B. et al. BMP type I receptor inhibition reduces heterotopic ossification. Nat. Med. 14, 1363–1369 (2008).10.1038/nm.1888 ↗
44. Schlessinger, J. et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mole. Cell 6, 743–750 (2000).10.1016/S1097-2765(00)00073-3 ↗
45. Eming, S. A., Martin, P. & Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med. 6, 265sr6 (2014).10.1126/scitranslmed.3009337 ↗
46. Jacques, L. B. Heparin: an old drug with a new paradigm. Science 206, 528–533 (1979).10.1126/science.386509 ↗
47. Petitou, M. & van Boeckel, C. A. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew. Chem. Int. Ed. 43, 3118–3133 (2004).10.1002/anie.200300640 ↗
48. Simmonds, M. C. et al. Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion. Ann. Intern. Med. 158, 877–889 (2013).10.7326/0003-4819-158-12-201306180-00005 ↗
49. Tovar, J. D., Claussen, R. C. & Stupp, S. I. Probing the interior of peptide amphiphile supramolecular aggregates. J. Am. Chem. Soc. 127, 7337–7345 (2005).10.1021/ja043764d ↗
50. Webber, M. J., Newcomb, C. J., Bitton, R. & Stupp, S. I. Switching of self-assembly in a peptide nanostructure with a specific enzyme. Soft Matter 7, 9665–9672 (2011).10.1039/c1sm05610g ↗
51. Gottlieb, H. E., Kotlyar, V. & Nudelman, A. NMR chemical shifts of common laboratory solvents as trace impurities. J. Org. Chem. 62, 7512–7515 (1997).10.1021/jo971176v ↗
52. Chen, B. et al. Carbohydrate rod conjugates: ternary rod−coil molecules forming complex liquid crystal structures. J. Am. Chem. Soc. 127, 16578–16591 (2005).10.1021/ja0535357 ↗
53. Eklind, K., Gustafsson, R., Tiden, A. K., Norberg, T. & Aberg, P. M. Large-scale synthesis of a Lewis b tetrasaccharide derivative, its acrylamide copolymer, and related di- and trisaccharides for use in adhesion inhibition studies with Helicobacter pylori. J. Carbohyd. Chem. 15, 1161–1178 (1996).10.1080/07328309608006504 ↗
54. Chernyak, A., Kononov, L. O. & Kochetkov, N. K. Synthesis of carbohydrate-amino acid conjugates related to the capsular antigen K54 from Escherichia coli O6:K54:H10 and artificial antigens therefrom. Carbohydr. Res. 216, 381–398 (1992).10.1016/0008-6215(92)84175-R ↗