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Glycosaminoglycan silencing by engineered CXCL12 variants

Lookup NU author(s): Professor Simi Ali


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We have engineered GPCR (G protein-coupled receptor) knock-out and high GAG-binding affinity into CXCL12 alpha to inhibit CXCL12 alpha-induced cell migration. Compared to wtCXCL12, the mutant CXCL12 alpha (Delta 8 L29K V39K) exhibited a 5.6-fold and a 2.2-fold affinity increase for heparin and heparan sulfate, respectively. From NaCl-based heparin displacement chromatography we concluded that more amino acid replacements would lead to altered GAG (glycosaminoglycan) ligand specificity. GAG silencing by this mutant was shown in a murine seeding model of human cancer cells, whereby a greatly reduced number of liver metastases was detected when the animals were treated intravenously with 1 mg/kg CXCL12 alpha (Delta 8 L29K V39K) before cancer cell application. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Gschwandtner M, Trinker MU, Hecher B, Adage T, Ali S, Kungl AJ

Publication type: Article

Publication status: Published

Journal: FEBS Letters

Year: 2015

Volume: 589

Issue: 19

Pages: 2819-2824

Print publication date: 14/09/2015

Online publication date: 20/08/2015

Acceptance date: 28/07/2015

ISSN (print): 0014-5793

ISSN (electronic): 1873-3468

Publisher: Elsevier


DOI: 10.1016/j.febslet.2015.07.052


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