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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Main Authors: Changye Sun, Mengxin Liu, Panwen Sun, Mingming Yang, Edwin A. Yates, Zhikun Guo, David G. Fernig
Format: Article
Language:English
Published: Wiley 2019-08-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12696
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spelling doaj-eb45c05452324b728998c57b928817652020-11-25T02:36:41ZengWileyFEBS Open Bio2211-54632019-08-01981477148710.1002/2211-5463.12696Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturationChangye Sun0Mengxin Liu1Panwen Sun2Mingming Yang3Edwin A. Yates4Zhikun Guo5David G. Fernig6Henan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University ChinaHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University ChinaHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University ChinaDepartment of Cardiology School of Medicine Affiliated Zhongda Hospital Southeast University Nanjing ChinaDepartment of Biochemistry Institute of Integrative Biology University of Liverpool UKHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University ChinaDepartment of Biochemistry Institute of Integrative Biology University of Liverpool UKFibroblast 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.https://doi.org/10.1002/2211-5463.12696differential scanning fluorimetryfibroblast growth factorprotein stabilitysulfated polysaccharide
collection DOAJ
language English
format Article
sources DOAJ
author Changye Sun
Mengxin Liu
Panwen Sun
Mingming Yang
Edwin A. Yates
Zhikun Guo
David G. Fernig
spellingShingle Changye Sun
Mengxin Liu
Panwen Sun
Mingming Yang
Edwin A. Yates
Zhikun Guo
David G. Fernig
Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
FEBS Open Bio
differential scanning fluorimetry
fibroblast growth factor
protein stability
sulfated polysaccharide
author_facet Changye Sun
Mengxin Liu
Panwen Sun
Mingming Yang
Edwin A. Yates
Zhikun Guo
David G. Fernig
author_sort Changye Sun
title 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_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_sort sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation
publisher Wiley
series FEBS Open Bio
issn 2211-5463
publishDate 2019-08-01
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.
topic differential scanning fluorimetry
fibroblast growth factor
protein stability
sulfated polysaccharide
url https://doi.org/10.1002/2211-5463.12696
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