16321-99-6Relevant articles and documents
A localized tolerance in the substrate specificity of the fluorinase enzyme enables "last-step" 18F fluorination of a RGD peptide under ambient aqueous conditions
Thompson, Stephen,Zhang, Qingzhi,Onega, Mayca,McMahon, Stephen,Fleming, Ian,Ashworth, Sharon,Naismith, James H.,Passchier, Jan,O'Hagan, David
, p. 8913 - 8918 (2014)
A strategy for last-step 18F fluorination of bioconjugated peptides is reported that exploits an "Achilles heel" in the substrate specificity of the fluorinase enzyme. An acetylene functionality at the C-2 position of the adenosine substrate projects from the active site into the solvent. The fluorinase catalyzes a transhalogenation of 5-chlorodeoxy-2- ethynyladenosine (ClDEA) to 5-fluorodeoxy-2-ethynyladenosine (FDEA). Extending a polyethylene glycol linker from the terminus of the acetylene allows the presentation of bioconjugation cargo to the enzyme for 18F labelling. The method uses an aqueous solution (H218O) of [ 18F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).
Synthesis and evaluation of 2-ethynyl-adenosine-5′-triphosphate as a chemical reporter for protein AMPylation
Creech, Christa,Kanaujia, Mukul,Causey, Corey P.
, p. 8550 - 8555 (2015)
Protein AMPylation is a posttranslational modification (PTM) defined as the transfer of an adenosine monophosphate (AMP) from adenosine triphosphate (ATP) to a hydroxyl side-chain of a protein substrate. One recently reported AMPylator enzyme, Vibrio outer protein S (VopS), plays a role in pathogenesis by AMPylation of Rho GTPases, which disrupts crucial signaling pathways, leading to eventual cell death. Given the resurgent interest in this modification, there is a critical need for chemical tools that better facilitate the study of AMPylation and the enzymes responsible for this modification. Herein we report the synthesis of 2-ethynyl-adenosine-5′-triphosphate (2eATP) and its utilization as a non-radioactive chemical reporter for protein AMPylation.
Photoinduced Alkylthiolation of Halogenated Purine Nucleosides
Nair, Vasu,Young, David A.
, p. 450 - 453 (1986)
A new highly efficient methodology for the synthesis of biologically important methylmercaptopurine nucleosides is described.The approach represents a substantial improvement over earlier reported methods for this class of compounds.
On the syntheses of 8-heteroaryl-substituted 9-(β-D-ribofuranosyl)-2,6-diaminopurines through Pd-catalyzed coupling in the presence of cupric oxide
Ozola,Persson,Gronowitz,Hornfeldt
, p. 863 - 866 (1995)
Convenient methods for the preparation of 9-(β-D-ribofuranosyl) derivatives of 8-(2- and 3-thienyl)-2,6-diaminopurine and of 8-(2- and 3-furyl)-2,6-diaminopurine, which are potential antiviral agents has been worked out. The key step was a Pd(0)-catalyzed Stille coupling between 2- and 3-tributylstannylthiophene and 2- and 3-tributylstannylfuran and trimethylsilyl protected 9-(β-D-ribofuranosyl)-2,6-diamino-8-bromopurine. The use of N,N-dimethylformamide as solvent at 110° and dichloro(diphenylphosphine-propane)palladium(II) [PdCl2(dppp)] with cupric oxide as co-reagent was essential in order to obtain a fast reaction and high yields.
Facile, chemoenzymatic synthesis of the potent antiviral compound, 2-acetonylinosine
Gupta, Mukta,Nair, Vasu
, p. 1165 - 1167 (2005)
A facile and efficient methodology for the chemoenzymatic synthesis of the antiviral compound, 2-acetonylinosine has been developed. The present synthetic strategy, which has generality, is a dramatic improvement on the methodologies currently available for the synthesis of functionalized purine nucleosides of therapeutic interest.
A facile synthesis of 2-azidoadenosine derivatives from guanosine as photoaffinity probes
Higashiya, Seiichiro,Kaibara, Chitose,Fukuoka, Koichiro,Suda, Fuminori,Ishikawa, Masahide,Yoshida, Masasuke,Hata, Tsujiaki
, p. 39 - 42 (1996)
2-Azidoadenosine (1) was synthesized in an overall yield of 49% from guanosine via the reaction of 9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-2-amino-6-chloropurine (2) with isoamyl nitrite and trimethylsilyl azide under neutral and anhydrous conditions. As photoaffinity probes, ATP analogues and the cap structure of eukaryotic mRNA bearing 2-azidoadenosine were synthesized.
Nucleic acid related compounds. 33. Conversions of adenosine and guanosine to 2,6-dichloro, 2-amino-6-chloro, and derived purine nucleosides
Robins,Uznanski
, p. 2601 - 2607 (1981)
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2-Substituted α,β-Methylene-ADP Derivatives: Potent Competitive Ecto-5′-nucleotidase (CD73) Inhibitors with Variable Binding Modes
Bhattarai, Sanjay,Pippel, Jan,Scaletti, Emma,Idris, Riham,Freundlieb, Marianne,Rolshoven, Georg,Renn, Christian,Lee, Sang-Yong,Abdelrahman, Aliaa,Zimmermann, Herbert,El-Tayeb, Ali,Müller, Christa E.,Str?ter, Norbert
supporting information, p. 2941 - 2957 (2020/04/10)
CD73 inhibitors are promising drugs for the (immuno)therapy of cancer. Here, we present the synthesis, structure-activity relationships, and cocrystal structures of novel derivatives of the competitive CD73 inhibitor α,β-methylene-ADP (AOPCP) substituted in the 2-position. Small polar or lipophilic residues increased potency, 2-iodo- and 2-chloro-adenosine-5′-O-[(phosphonomethyl)phosphonic acid] (15, 16) being the most potent inhibitors with Ki values toward human CD73 of 3-6 nM. Subject to the size and nature of the 2-substituent, variable binding modes were observed by X-ray crystallography. Depending on the binding mode, large species differences were found, e.g., 2-piperazinyl-AOPCP (21) was >12-fold less potent against rat CD73 compared to human CD73. This study shows that high CD73 inhibitory potency can be achieved by simply introducing a small substituent into the 2-position of AOPCP without the necessity of additional bulky N6-substituents. Moreover, it provides valuable insights into the binding modes of competitive CD73 inhibitors, representing an excellent basis for drug development.
Essential Structural Profile of Novel Adenosine Derivatives as Antiplatelet Aggregation Inhibitors Based on 3D-QSAR Analysis Using CoMFA, CoMSIA, and SOMFA
Bao, XueFeng,Du, Hongguang,Liu, Guocheng,Lu, Chenghu,Ren, Chaorui,Shunlai, Li
, p. 448 - 457 (2020/06/30)
Abstact: —In this study, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and the self-organizing molecular field analysis (SOMFA) were performed on a series of novel adenosine derivatives. Significant correlation coefficients (CoMFA, q2 = 0.560, r2 = 0.940, F value = 71.850, and SEE = 0.097; CoMSIA, q2 = 0.528, r2 = 0.943, F value = 29.29 and SEE = 0.108; SOMFA, r2 = 0.615, r2cr= 0.577, F value = 60.797, and SEE = 0.226) were obtained, and the generated models were validated using test sets. By analyzing the corresponding contour maps in detail, new adenosine derivatives with potential efficacy were designed for synthesis in the future.
S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation
McKean, Iain J. W.,Sadler, Joanna C.,Cuetos, Anibal,Frese, Amina,Humphreys, Luke D.,Grogan, Gideon,Hoskisson, Paul A.,Burley, Glenn A.
supporting information, p. 17583 - 17588 (2019/11/11)
A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5′-chloro-5′-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.
