Structure Activity Relationship of Heparin Mimicking Polymer p(SS- co -PEGMA): Effect of Sulfonation and Polymer Size on FGF2-Receptor Binding.

Autor:	Paluck SJ; Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States., Maynard HD; Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
Jazyk:	angličtina
Zdroj:	Polymer chemistry [Polym Chem] 2017 Aug 20; Vol. 8 (31), pp. 4548-4556. Date of Electronic Publication: 2017 Jul 05.
DOI:	10.1039/C7PY00861A
Abstrakt:	Fibroblast growth factor-2 (FGF2) is a heparin binding protein that plays a role in a range of biological functions such as wound healing and bone regeneration. Heparin, a highly sulfated glycosaminoglycan, is required for FGF2 to bind to its receptor. Therefore, polymeric mimics of heparin are widely studied for their ability to manipulate FGF2-induced biological interactions. It is known that altering the degree of sulfonated monomer incorporation and size of heparin-mimicking polymers can affect protein-receptor binding. To elucidate the relationship between degree of sulfonation and receptor binding for the heparin-mimicking polymer, poly(styrene sulfonate- co -poly(ethylene glycol) methyl ether methacrylate) (p(SS- co -PEGMA)) a library was synthesized to contain nine polymers with degrees of sulfonation ranging from 0-100%. Kinetics of the polymerization was evaluated and reactivity ratios compared to literature results. These polymers were then tested for their ability to enhance FGF2 binding with its receptor as both covalent conjugates and as excipients. In a receptor based enzyme-linked immunosorbant assay (ELISA), as well as a cell-based study, the polymer with 81% SS incorporation enhanced receptor binding compared to FGF2 alone, and to a greater extent than the other polymers. Therefore, another library of polymers was prepared maintaining the degree of sulfonation at 81% and changing the size from 41 to 390 monomer repeat units. The polymers were again tested in receptor based ELISA and cell studies, and all of the different sizes performed similarly, except for degree of polymerization 295 and 390, which had reduced response in the cellular assay. These results provide important information for the use of pSS- co -PEGMA as a potential heparin-mimicking therapeutic. Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.
Databáze:	MEDLINE
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