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dc.contributor.authorFarrell, Nicholas P
dc.contributor.authorGorle, Anil K
dc.contributor.authorPeterson, Erica J
dc.contributor.authorBerners-Price, Susan J
dc.contributor.editorSigel, A
dc.contributor.editorSigel, H
dc.contributor.editorFreisinger, E
dc.contributor.editorSigel, RKO
dc.date.accessioned2019-07-11T12:31:20Z
dc.date.available2019-07-11T12:31:20Z
dc.date.issued2018
dc.identifier.isbn978-3-11-046984-4
dc.identifier.doi10.1515/9783110470734-004
dc.identifier.urihttp://hdl.handle.net/10072/377954
dc.description.abstractGlycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) are large complex carbohydrate molecules that bind to a wide variety of proteins and exercise important physiological and pathological processes. This chapter focuses on the concept of metalloglycomics and reviews the structure and conformation of GAGs and the role of various metal ions during the interaction of GAGs with their biological partners such as proteins and enzymes. The use of metal complexes in heparin analysis is discussed. Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase modulates tumor-related events including angiogenesis, cell invasion, metastasis, and inflammation. HS is identified as a ligand receptor for polynuclear platinum complexes (PPCs) defining a new mechanism of cellular accumulation for platinum drugs with implications for tumor selectivity. The covalent and noncovalent interaction of PPCs with GAGs and the functional consequences of strong binding with HS are explained in detail. Sulfate cluster anchoring shields the sulfates from recognition by charged protein residues preventing the exercise of the HS-enzyme/protein function, such as growth factor recognition and the activity of heparanase on HS. The cellular consequences are inhibition of invasion and angiogenesis. Metalloglycomics is a potentially rich new area of endeavor for bioinorganic chemists to study the relevance of intrinsic metal ions in heparin/ HS-protein interactions and for development of new compounds for therapeutic, analytical, and imaging applications.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherWalter de Gruyter GmbH
dc.publisher.placeGermany
dc.relation.ispartofbooktitleMetallo-Drugs: Development and Action of Anticancer Agents
dc.relation.ispartofchapter4
dc.relation.ispartofchapternumbers17
dc.relation.ispartofpagefrom109
dc.relation.ispartofpageto140
dc.subject.fieldofresearchOther chemical sciences not elsewhere classified
dc.subject.fieldofresearchcode349999
dc.titleMetalloglycomics
dc.typeBook chapter
dc.type.descriptionB2 - Chapters (Other)
dc.type.codeB - Book Chapters
gro.hasfulltextNo Full Text
gro.griffith.authorBerners-Price, Sue J.


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