Semi-preparative high-performance countercurrent chromatography method for the purification of chemically synthesized ATP analogue, ApppI

Puljula, Elina; Turhanen, Petri A.

doi:10.1016/j.jchromb.2017.08.038

Cited by 10 publications

(20 citation statements)

References 11 publications

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“…The overall yield for ApppD was only about 21%; this is reasonable for this kind of compound and comparable to the results reported elsewhere for ApppI. 12 − 14 …”

Section: Results and Discussionsupporting

confidence: 90%

“…The crude reaction mixture was successfully purified by high-performance countercurrent chromatography (HPCCC) using exactly the same method described elsewhere. 14 Interestingly, the method reported here for the synthesis of ApppD also resulted in the formation of 1-adenosin-5′-yl 3-(3-methylbut-2-enyl) diphosphoric acid diester (AppD; see the structure in Figure 3 ); this compound could be isolated by HPCCC purification of the crude reaction mixture as a side-product (see HPCCC chromatogram in the Supporting Information ). The observed ratio of TBA/ApppD was higher than the ratio of TBA/ATP used in the synthesis, and it can be different in the different HPCCC runs.…”

Section: Results and Discussionmentioning

confidence: 90%

“…An HPCCC method reported elsewhere was used in the purification of ApppD and AppD. 14 Mass spectra were recorded on a quadrupole time-of-flight mass spectrometer (qTOF-MS) using electrospray ionization (ESI) in the negative ionization mode. The purity of the products was determined from 1 H and 31 P NMR spectra and was ≥95% unless stated otherwise.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The crude product was purified by exactly the same HPCCC method as utilized in the purification of ApppI. 14 Appropriate fractions were collected and evaporated to dryness in vacuo (see HPCCC chromatogram in the Supporting Information as an example). ApppD × 4.1 TBA salt (117 mg, 21%) was obtained as a colorless solid (highly hygroscopic!).…”

Section: Experimental Sectionmentioning

confidence: 99%

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Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD

Turhanen

2017

ACS Omega

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The chemical synthesis of a adenosine triphosphate analogue, 1-adenosin-5′-yl 3-(3-methylbut-2-enyl) triphosphoric acid diester (ApppD), is described. ApppD is known to be an active metabolite of the mevalonate pathway in the human body like its structural isomer isopentenyl ester of ATP (ApppI). Very recently, ApppI has been found to possess novel function(s); now it will also be possible to examine the effects of ApppD more precisely because it can be synthesized in reasonable amounts. 1-Adenosin-5′-yl 3-(3-methylbut-2-enyl) diphosphoric acid diester (AppD; a adenosine diphosphate analogue) was also isolated from the synthesis mixture. Both ApppD and AppD were characterized by 1H, 13C, 31P NMR and mass spectrometry methods.

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“…The overall yield for ApppD was only about 21%; this is reasonable for this kind of compound and comparable to the results reported elsewhere for ApppI. 12 − 14 …”

Section: Results and Discussionsupporting

confidence: 90%

Section: Results and Discussionmentioning

confidence: 90%

Section: Experimental Sectionmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

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Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD

Turhanen

2017

ACS Omega

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“…So, ApppI is a more potent EGFR inhibitor than any of the bisphosphonates tested or indeed the ATP analog AMP·PNP, which has an IC 50 of 36 μM in this assay. We also prepared and tested the dimethylallyl ester of ATP, ApppD ( 12 ), , finding an IC 50 ≈ 14 μM (Figure S1).…”

Section: Results and Discussionmentioning

confidence: 99%

Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways

et al. 2018

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Bisphosphonates are a major class of drugs used to treat osteoporosis, Paget's disease, and cancer. They have been proposed to act by inhibiting one or more targets including protein prenylation, the epidermal growth factor receptor, or the adenine nucleotide translocase. Inhibition of the latter is due to formation in cells of analogs of ATP: the isopentenyl ester of ATP (ApppI) or an AppXp-type analog of ATP, such as AMP-clodronate (AppCClp). We screened both ApppI as well as AppCClp against a panel of 369 kinases finding potent inhibition of some tyrosine kinases by AppCClp, attributable to formation of a strong hydrogen bond between tyrosine and the terminal phosphonate. We then synthesized bisphosphonate preprodrugs that are converted in cells to other ATP-analogs, finding low nM kinase inhibitors that inhibited cell signaling pathways. These results help clarify our understanding of the mechanisms of action of bisphosphonates, potentially opening up new routes to the development of bone resorption, anticancer, and anti-inflammatory drug leads.

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Simultaneous separation of six pure polymethoxyflavones from sweet orange peel extract by high performance counter current chromatography

Yang

et al. 2019

Food Chemistry

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Semi-preparative high-performance countercurrent chromatography method for the purification of chemically synthesized ATP analogue, ApppI

Cited by 10 publications

References 11 publications

Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD

Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD

Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways

Simultaneous separation of six pure polymethoxyflavones from sweet orange peel extract by high performance counter current chromatography

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