Maria Arkel published latest article in Medicinal chemistry (Shariqah (United Arab Emirates)) entitled A Novel Method to Synthesize Phosphocreatine and Phosphocreatine Prodrugs. This article is available in PubMed with an unique identification number PMID: 29165089 and it is published in 2017. The coauthors of this article are Arkel M; Garbati P; Salis A; Damonte G; Liessi N; Adriano E; Benatti U; Balestrino M; Millo E.
Co-Author(s): Arkel M; Garbati P; Salis A; Damonte G; Liessi N; Adriano E; Benatti U; Balestrino M; Millo E
Affiliation(s): Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa. Italy.
PMID 29165089, Year 2017
Abstract: Background Adenosine triphosphate (ATP) is the energy currency of the body; it takes part in various and indispensable metabolic processes for the maintenance of cell homeostasis, degrading to its hydrolysis product, adenosine diphosphate (ADP). Efficient ways to restore ATP are therefore necessary in the cells. When the cell lacks energy due to ischemic conditions or high ATP demand, phosphocreatine gives its phosphate group to ADP that converts to ATP, in a reaction catalyzed by the enzyme creatine kinase. For this reason, phosphocreatine is utilized as a pharmacological treatment in human diseases that involve a failure of the cellular energy, most notably in coronary artery disease. Objective Commercially available phosphocreatine is currently synthesized using different methods, each of one characterized by a rather low yield of the final product, probably due to the low reactivity of the guanylating reagent. The aim of this work is to overcome the drawbacks of the synthetic methods currently employed, devising a novel synthetic route to obtain phosphocreatine and phosphocreatine prodrugs in higher yields and purity. Method To obtain an higher yield of the final product and a lower number of sub-products, this method utilizes a new guanylating agent characterized by high reactivity, endowed with a protecting group t-Boc on one of the two nitrogen atoms of the guanidinic function and a protected phosphate on the other one; that compound is then conjugated with an opportune secondary ammine. The obtained product is cleaved first with acidic conditions to obtain the phosphocreatine prodrug (phosphocreatine ethyl ester) and then with an enzymatic method to obtain the phosphocreatine Results Both the phosphocreatine prodrug and the phosphocreatine have been obtained in good yield and purity as demonstrated by HPLC and mass spectrometry analysis. Conclusion This novel synthetic route permits to obtain the phosphocreatine molecule in higher yield and purity compared to the methods currently employed with a combination of chemical and enzymatic methods.
Journal: Medicinal chemistry (Shariqah (United Arab Emirates))
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