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Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation

Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturat...

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Autores principales: Sun, Changye, Liu, Mengxin, Sun, Panwen, Yang, Mingming, Yates, Edwin A., Guo, Zhikun, Fernig, David G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668377/
https://www.ncbi.nlm.nih.gov/pubmed/31271519
http://dx.doi.org/10.1002/2211-5463.12696
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author Sun, Changye
Liu, Mengxin
Sun, Panwen
Yang, Mingming
Yates, Edwin A.
Guo, Zhikun
Fernig, David G.
author_facet Sun, Changye
Liu, Mengxin
Sun, Panwen
Yang, Mingming
Yates, Edwin A.
Guo, Zhikun
Fernig, David G.
author_sort Sun, Changye
collection PubMed
description Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturation at ambient temperatures and during long‐time storage, which will reduce their biological activity. The interaction of FGFs with the sulfated domains of heparan sulfate and heparin is essential for their cellular signaling and stability. Therefore, we analyzed the interactions of FGF1 and FGF2 with four sulfated polysaccharides: heparin, dextran sulfate (DXS), λ‐carrageenan, and chondroitin sulfate. The results of thermal stability and cell proliferation assays demonstrate that heparin, DXS, and λ‐carrageenan bound to both FGFs and protected them from denaturation. Our results suggest heparin, DXS, and λ‐carrageenan are potential formulation materials that bind and stabilize FGFs, and which may also potentiate their activity and control their delivery.
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spelling pubmed-66683772019-08-06 Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation Sun, Changye Liu, Mengxin Sun, Panwen Yang, Mingming Yates, Edwin A. Guo, Zhikun Fernig, David G. FEBS Open Bio Research Articles Fibroblast growth factors (FGFs) regulate embryonic development and homeostasis, including tissue and organ repair and specific aspects of metabolism. The basic FGF and acidic FGF, now known as FGF2 and FGF1, are widely used protein drugs for tissue repair. However, they are susceptible to denaturation at ambient temperatures and during long‐time storage, which will reduce their biological activity. The interaction of FGFs with the sulfated domains of heparan sulfate and heparin is essential for their cellular signaling and stability. Therefore, we analyzed the interactions of FGF1 and FGF2 with four sulfated polysaccharides: heparin, dextran sulfate (DXS), λ‐carrageenan, and chondroitin sulfate. The results of thermal stability and cell proliferation assays demonstrate that heparin, DXS, and λ‐carrageenan bound to both FGFs and protected them from denaturation. Our results suggest heparin, DXS, and λ‐carrageenan are potential formulation materials that bind and stabilize FGFs, and which may also potentiate their activity and control their delivery. John Wiley and Sons Inc. 2019-07-16 /pmc/articles/PMC6668377/ /pubmed/31271519 http://dx.doi.org/10.1002/2211-5463.12696 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sun, Changye
Liu, Mengxin
Sun, Panwen
Yang, Mingming
Yates, Edwin A.
Guo, Zhikun
Fernig, David G.
Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title_full Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title_fullStr Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title_full_unstemmed Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title_short Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
title_sort sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668377/
https://www.ncbi.nlm.nih.gov/pubmed/31271519
http://dx.doi.org/10.1002/2211-5463.12696
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