Reconsideration of Serum Ti(IV) Transport: Albumin and Transferrin Trafficking of Ti(IV) and Its Complexes.
The trafficking of titanium(IV) by human serum transferrin (HsTf) has been implicated in the physiology of this hydrolysis-prone metal. The current work broadens to include the further interactions of Ti(IV) in serum that bear on this model. TiHsTf (2 equiv) binds the transferrin receptor TfR1 with...
| Publicado en: | Journal of the American Chemical Society Vol. 130; no. 7; pp. 2262 - 2271 |
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| Autores principales: | , , |
| Formato: | Artículo |
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American Chemical Society
2/20/2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=31215068&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 31215068 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 2/20/2008 vid: 130 iid: 7 pid: 997 pub: American Chemical Society artinfo: ui: 31215068 10.1021/ja076364+ ppf: 2262 ppct: 9 formats: tig: atl: Reconsideration of Serum Ti(IV) Transport: Albumin and Transferrin Trafficking of Ti(IV) and Its Complexes. aug: au: Tinoco, Arthur D. Eames, Emily V. Valentine, Ann M. affil: Department of Chemistry, Yale University, P.O. Box 208/07, New Haven, Connecticut 06520-8107 su: Serum albumin Titanium Transferrin Carrier proteins Ligands (Chemistry) Biochemistry sug: subj: Serum albumin Titanium Transferrin Carrier proteins Ligands (Chemistry) Biochemistry ab: The trafficking of titanium(IV) by human serum transferrin (HsTf) has been implicated in the physiology of this hydrolysis-prone metal. The current work broadens to include the further interactions of Ti(IV) in serum that bear on this model. TiHsTf (2 equiv) binds the transferrin receptor TfR1 with K = 6.3 ± 0.4 nM and K = 410 ± 150 nM, values that are the tightest yet measured for a metal other than iron but weaker than the corresponding ones for FeHsTf due to both slightly slower on rates and slightly faster off rates. Comparing the affinities of metals for HsTf with the affinities of the resulting MHsTf species for TfR1, we speculate that the formation of an MHsTf complex of high affinity may predict a lobe-closed conformation that leads to a favorable interaction with TfR1. Human serum albumin (HSA), an important serum competitor for metal binding, can bind up to 20 equiv of Ti(lV) supplied in several forms. With some ligands, Ti(lV) may bind to the N-terminal metal binding site of albumin, forming a ternary complex. However, the dominant type of HSA binding is via Ti(lV) in complex form, probably at surface sites. Notably, HSA greatly stabilizes the titanocene moiety of the drug candidate CpTiCl with respect to hydrolysis and precipitation. HSA binds Ti(IV) citrate supplied as a hydrolyzed or unhydrolyzed source, with 1 equiv of citrate remaining bound. Titanium(IV) monocitrate neither competes with the binding of reporter molecules known to dock at canonical drug sites I or II nor binds at the N-terminus. HsTf outcompetes HSA for soluble Ti(IV) in a direct competition, but once bound to albumin, the transfer of Ti(lV) from HSA to HsTf is quite slow. Each of these findings has implications for the metabolism of Ti(lV) in human serum. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2008 holdings: @attributes: islocal: N |
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