Conformational Modulation of Iduronic Acid-Containing Sulfated Glycosaminoglycans by a Polynuclear Platinum Compound and Implications for Development of Antimetastatic Platinum Drugs.

Autor: Gorle AK; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia., Haselhorst T; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia., Katner SJ; Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA.; Department of Biochemistry, Chemistry and Geology, Minnesota State University, Mankato, Mankato, MN, 56001, USA., Everest-Dass AV; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia., Hampton JD; Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA.; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA., Peterson EJ; Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA.; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA., Koblinski JE; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA.; Department of Pathology, Division of Cellular and Molecular Pathogenesis, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA., Katsuta E; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, NY, 14203, USA., Takabe K; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, NY, 14203, USA., von Itzstein M; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia., Berners-Price SJ; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia., Farrell NP; Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, Queensland, 4222, Australia.; Department of Chemistry, Virginia Commonwealth University, Richmond, VA, 23284-2006, USA.; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 23298-0037, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Feb 08; Vol. 60 (6), pp. 3283-3289. Date of Electronic Publication: 2020 Dec 23.
DOI: 10.1002/anie.202013749
Abstrakt: 1 H NMR spectroscopic studies on the 1:1 adduct of the pentasaccharide Fondaparinux (FPX) and the substitution-inert polynuclear platinum complex TriplatinNC show significant modulation of geometry around the glycosidic linkages of the FPX constituent monosaccharides. FPX is a valid model for the highly sulfated cell signalling molecule heparan sulfate (HS). The conformational ratio of the 1 C 4 : 2 S 0 forms of the FPX residue IdoA(2S) is altered from ca. 35:65 (free FPX) to ca. 75:25 in the adduct; the first demonstration of a small molecule affecting conformational changes on a HS oligosaccharide. Functional consequences of such binding are suggested to be inhibition of HS cleavage in MDA-MB-231 triple-negative breast cancer (TNBC) cells. We further describe inhibition of metastasis by TriplatinNC in the TNBC 4T1 syngeneic tumour model. Our work provides insight into a novel approach for design of platinum drugs (and coordination compounds in general) with intrinsic anti-metastatic potential.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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