Comparison of Metal-Ammine Compounds Binding to DNA and Heparin. Glycans as Ligands in Bioinorganic Chemistry
| Autor: | Wyatt E. Johnson, Phillip Page, Nicholas P. Farrell, Samantha J. Katner, Erica J. Peterson |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Organoplatinum Compounds
Swine 010402 general chemistry Ligands 01 natural sciences Fluorescence Ruthenium Coordination complex Inorganic Chemistry chemistry.chemical_compound Coordination Complexes Moiety Animals Physical and Theoretical Chemistry Surface plasmon resonance Amines Fluorescent Dyes Platinum chemistry.chemical_classification 010405 organic chemistry Oligonucleotide Heparin Rhodamines Isothermal titration calorimetry Bioinorganic chemistry Hydrogen Bonding Heparan sulfate Cobalt DNA Combinatorial chemistry 0104 chemical sciences Methylene Blue chemistry Ethidium bromide |
| Zdroj: | Inorganic chemistry. 57(6) |
| ISSN: | 1520-510X |
| Popis: | We present spectroscopic and biophysical approaches to examine the affinity of metal-ammine coordination complexes for heparin as a model for heparan sulfate (HS). Similar to nucleic acids, the highly anionic nature of heparin means it is associated in vivo with physiologically relevant cations, and this work extends their bioinorganic chemistry to substitution-inert metal-ammine compounds (M). Both indirect and direct assays were developed. M compounds are competitive inhibitors of methylene blue (MB)-heparin binding, and the change in the absorbance of the dye in the presence or absence of heparin can be used as an indirect reporter of M-heparin affinity. A second indirect assay uses the change in fluorescence of TAMRA-R9, a nonaarginine linked to a fluorescent TAMRA moiety, as a reporter for M-heparin binding. Direct assays are surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The Kd values for TriplatinNC-heparin varied to some extent depending on the technique from 33.1 ± 2 nM (ITC) to 66.4 ± 1.3 nM (MB absorbance assay) and 340 ± 30 nM (SPR). The differences are explained by the nature of the technique and the use of heparin of differing molecular weight. Indirect probes using the displacement of ethidium bromide from DNA or, separately, fluorescently labeled oligonucleotide (DNA-Fl) can measure the relative affinities of heparin and DNA for M compounds. These assays showed essentially equivalent affinity of TriplatinNC for heparin and DNA. The generality of these methods was confirmed with a series of mononuclear cobalt, ruthenium, and platinum compounds with significantly lower affinity because of their smaller overall positive charge but in the order [Co(NH3)6]3+ > [Ru(NH3)6]3+ > [Pt(NH3)4]2+. The results on heparin can be extrapolated to glycosoaminoglycans such as HS, emphasizing the relevance of glycan interactions in understanding the biological properties of coordination compounds and the utility of the metalloglycomics concept for extending bioinorganic chemistry to this class of important biomolecules. |
| Databáze: | OpenAIRE |
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