Conformational Modulation of Iduronic Acid-Containing Sulfated Glycosaminoglycans by a Polynuclear Platinum Compound and Implications for Development of Antimetastatic Platinum Drugs.
Angew Chem Int Ed Engl
; 60(6): 3283-3289, 2021 02 08.
Article
em En
| MEDLINE
| ID: mdl-33174390
ABSTRACT
1 Hâ
NMR spectroscopic studies on the 11 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 C42 S0 forms of the FPX residue IdoA(2S) is altered from ca. 3565 (free FPX) to ca. 7525 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.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
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Platina
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Glicosaminoglicanos
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Ácido Idurônico
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Antineoplásicos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article