8-Azapurines as substrates for the E. coli purine nucleoside phosphorylase – II (xanthosine phosphorylase): Does the ribosylation always go to the aza-purine N(9)?

2005 ◽  
Author(s):  
Borys Kierdaszuk ◽  
Jacek Wierzchowski
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
E Coli

scholarly journals Radical Dehalogenation and Purine Nucleoside Phosphorylase E. coli: How Does an Admixture of 2′,3′-Anhydroinosine Hinder 2-fluoro-cordycepin Synthesis

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 539
Author(s):  
Alexey L. Kayushin ◽  
Julia A. Tokunova ◽  
Ilja V. Fateev ◽  
Alexandra O. Arnautova ◽  
Maria Ya. Berzina ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Chemical Synthesis ◽  
Purine Nucleoside Phosphorylase ◽  
Purine Nucleoside ◽  
Preparative Synthesis ◽  
Nucleoside Phosphorylase ◽  
E Coli ◽  
First Time

During the preparative synthesis of 2-fluorocordycepin from 2-fluoroadenosine and 3′-deoxyinosine catalyzed by E. coli purine nucleoside phosphorylase, a slowdown of the reaction and decrease of yield down to 5% were encountered. An unknown nucleoside was found in the reaction mixture and its structure was established. This nucleoside is formed from the admixture of 2′,3′-anhydroinosine, a byproduct in the preparation of 3-′deoxyinosine. Moreover, 2′,3′-anhydroinosine forms during radical dehalogenation of 9-(2′,5′-di-O-acetyl-3′-bromo- -3′-deoxyxylofuranosyl)hypoxanthine, a precursor of 3′-deoxyinosine in chemical synthesis. The products of 2′,3′-anhydroinosine hydrolysis inhibit the formation of 1-phospho-3-deoxyribose during the synthesis of 2-fluorocordycepin. The progress of 2′,3′-anhydroinosine hydrolysis was investigated. The reactions were performed in D2O instead of H2O; this allowed accumulating intermediate substances in sufficient quantities. Two intermediates were isolated and their structures were confirmed by mass and NMR spectroscopy. A mechanism of 2′,3′-anhydroinosine hydrolysis in D2O is fully determined for the first time.

scholarly journals In vivo sensitization of ovarian tumors to chemotherapy by expression of E. coli purine nucleoside phosphorylase in a small fraction of cells

Gene Therapy ◽  
2000 ◽  
Vol 7 (20) ◽  
pp. 1738-1743 ◽  
Author(s):  
V K Gadi ◽  
S D Alexander ◽  
J E Kudlow ◽  
P Allan ◽  
W B Parker ◽  
...  
Keyword(s):  
Purine Nucleoside Phosphorylase ◽  
Ovarian Tumors ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
E Coli

scholarly journals Identification of a Subversive Substrate of Trichomonas vaginalis Purine Nucleoside Phosphorylase and the Crystal Structure of the Enzyme-Substrate Complex

2005 ◽  
Vol 280 (23) ◽  
pp. 22318-22325 ◽  
Author(s):  
Yang Zang ◽  
Wen-Hu Wang ◽  
Shaw-Wen Wu ◽  
Steven E. Ealick ◽  
Ching C. Wang
Keyword(s):  
Active Site ◽  
Trichomonas Vaginalis ◽  
Purine Nucleoside Phosphorylase ◽  
Quaternary Structure ◽  
Transmitted Disease ◽  
Purine Nucleoside ◽  
Purine Base ◽  
Nucleoside Phosphorylase ◽  
E Coli

Trichomonas vaginalis is an anaerobic protozoan parasite that causes trichomoniasis, a common sexually transmitted disease with worldwide impact. One of the pivotal enzymes in its purine salvage pathway, purine nucleoside phosphorylase (PNP), shows physical properties and substrate specificities similar to those of the high molecular mass bacterial PNPs but differing from those of human PNP. While carrying out studies to identify inhibitors of T. vaginalis PNP (TvPNP), we discovered that the nontoxic nucleoside analogue 2-fluoro-2′-deoxyadenosine (F-dAdo) is a “subversive substrate.” Phosphorolysis by TvPNP of F-dAdo, which is not a substrate for human PNP, releases highly cytotoxic 2-fluoroadenine (F-Ade). In vitro studies showed that both F-dAdo and F-Ade exert strong inhibition of T. vaginalis growth with estimated IC50 values of 106 and 84 nm, respectively, suggesting that F-dAdo might be useful as a potential chemotherapeutic agent against T. vaginalis. To understand the basis of TvPNP specificity, the structures of TvPNP complexed with F-dAdo, 2-fluoroadenosine, formycin A, adenosine, inosine, or 2′-deoxyinosine were determined by x-ray crystallography with resolutions ranging from 2.4 to 2.9 Å. These studies showed that the quaternary structure, monomer fold, and active site are similar to those of Escherichia coli PNP. The principal active site difference is at Thr-156, which is alanine in E. coli PNP. In the complex of TvPNP with F-dAdo, Thr-156 causes the purine base to tilt and shift by 0.5 Å as compared with the binding scheme of F-dAdo in E. coli PNP. The structures of the TvPNP complexes suggest opportunities for further improved subversive substrates beyond F-dAdo.

Open and closed conformation of the E. coli purine nucleoside phosphorylase active center and implications for the catalytic mechanism

2002 ◽  
Vol 315 (3) ◽  
pp. 351-371 ◽  
Author(s):  
Gertraud Koellner ◽  
Agnieszka Bzowska ◽  
Beata Wielgus-Kutrowska ◽  
Marija Luić ◽  
Thomas Steiner ◽  
...  
Keyword(s):  
Active Center ◽  
Purine Nucleoside Phosphorylase ◽  
Catalytic Mechanism ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
E Coli ◽  
Closed Conformation
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