19F NMR applications in chemical biology

Cobb, Steven L.; Murphy, Cormac D.

doi:10.1016/j.jfluchem.2008.11.003

Cited by 152 publications

(115 citation statements)

References 131 publications

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“…In the following years, fluorinated amino acids became a widely used tool in structural NMR analysis of proteins. [45][46][47][48][49][50][51] Also in the 1970s, the first experiments using 2-fluorohistidine ((2-F)His) for protein biosynthesis were reported. Its biological effects and its incorporation into (mammalian) proteins were studied.…”

Section: Biological Incorporation Of Fluorinated Amino Acids Into Pepmentioning

confidence: 99%

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Merkel

Budiša

2012

Org. Biomol. Chem.

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Section: Biological Incorporation Of Fluorinated Amino Acids Into Pepmentioning

confidence: 99%

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Merkel

Budiša

2012

Org. Biomol. Chem.

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“…The assignment of the fluorine resonances is useful when, for example, studying metabolism or complexation of the molecule. [42,43] Compound 3 presents a 1D 19 F spectrum with two resonances that consist of a dt at −125.3 ppm and a ddd at −138.9 ppm. In the HETCOR spectrum (Fig.…”

Section: Assignment Of Diastereotopic Fluorine Atomsmentioning

confidence: 99%

Application of fluorine NMR for structure identification of steroids

Ampt

Aspers

Jaeger

et al. 2011

Magnetic Reson in Chemistry

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Fluorinated steroids were examined using 1D and 2D homo- and heteronuclear (19)F NMR, such as (19)F-(1) H and (19)F-(13)C. The utilization of fluorine NMR accounted for spectral simplification and resulted in a straightforward pathway for the determination of structures including the configuration of these compounds; these steroids present an illustrative example for other types of fluorinated compounds, which are increasingly encountered in drug discovery. The potential of (19)F NMR is elaborated on in detail for two compounds containing diastereotopic fluorines with different coupling patterns. The analysis of the coupling patterns and the through-space interactions resulted in the determination of the structure and configuration. Heteronuclear correlation experiments, i.e. (19)F-(1)H HETCOR, (19)F-(13)C HMQC and HMBC, and (19)F-(1)H HOESY, were applied to determine first the relative stereochemistry and then the molecular configuration at C4 and C5 of a steroidal compound bearing a fused three-membered ring with two fluorine substituents. These examples proved (19)F NMR to be a useful addition to the extensively used (1)H and (13)C NMR within structure elucidation and configuration determination of small molecules.

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“…Fluorine can also be strategically incorporated to provide novel biochemical tools that are useful for the development of TTDDSs [15, 34]. For instance, by taking advantage of the fact that the fluorine nucleus is virtually non-existent in biological systems, 19 F NMR can provide techniques to directly observe time-dependent processes in complex biological systems [35]. …”

Section: Introductionmentioning

confidence: 99%

Strategic incorporation of fluorine into taxoid anticancer agents for medicinal chemistry and chemical biology studies

Ojima

2017

Journal of Fluorine Chemistry

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This account exemplifies our recent progress on the strategic incorporation of fluorine and organofluorine groups to taxoid anticancer agents and their tumor-targeted drug delivery systems (TTDDSs) for medicinal chemistry and chemical biology studies. Novel 3′-difluorovinyltaxoids were strategically designed to block the metabolism by cytochrome P-450, synthesized, and evaluated for their cytotoxicity against drug-sensitive and multidrug-resistant (MDR) human cancer cell lines. 3′-Difluorovinyltaxoids exhibited impressive activities against these cancer cell lines. More significantly, a representative 3′-difluorovinyltaxoid exhibited 230-33,000 times higher potency than conventional anticancer drugs against cancer stem cell-enriched HCT-116 cell line. Studies on the mechanism of action (MOA) of these fluorotaxoids were performed by tubulin polymerization assay, morphology analysis by electron microscopy (EM) and protein binding assays. Novel 19F NMR probes, BLT-F2 and BLT-S-F6, were designed by strategically incorporating fluorine, CF3 and CF3O groups into tumor-targeting drug conjugates. These 19F-probes were designed and synthesized to investigate the mechanism of linker cleavage and factors that influence their plasma and metabolic stability by real-time 19F NMR analysis. Time-resolved 19F NMR study on probe BLT-F2 revealed a stepwise mechanism for the release of a fluorotaxoid, which might not be detected by other analytical methods. Probe BLT-S-F6 were very useful to study the stability and reactivity of the drug delivery system in human blood plasma by 19F NMR. The clean analysis of the linker stability and reactivity of drug conjugates in blood plasma by HPLC and 1H NMR is very challenging, but the use of 19F NMR and suitable 19F probes can provide a practical solution to this problem.

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19F NMR applications in chemical biology

Cited by 152 publications

References 131 publications

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Organic fluorine as a polypeptide building element: in vivo expression of fluorinated peptides, proteins and proteomes

Application of fluorine NMR for structure identification of steroids

Strategic incorporation of fluorine into taxoid anticancer agents for medicinal chemistry and chemical biology studies

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