38874-35-0Relevant articles and documents
Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route
Vyskocil, Stepan,Cardin, David,Ciavarri, Jeffrey,Conlon, Joe,Cullis, Courtney,England, Dylan,Gershman, Rachel,Gigstad, Kenneth,Gipson, Krista,Gould, Alexandra,Greenspan, Paul,Griffin, Robert,Gulavita, Nanda,Harrison, Sean,Hu, Zhigen,Hu, Yongbo,Hata, Akito,Huang, Jian,Huang, Shih-Chung,Janowick, Dave,Jones, Matthew,Kolev, Vihren,Langston, Steven P.,Lee, Hong Myung,Li, Gang,Lok, David,Ma, Liting,Mai, Doanh,Malley, Jenna,Matsuda, Atsushi,Mizutani, Hirotake,Mizutani, Miho,Molchanova, Nina,Nunes, Elise,Pusalkar, Sandeep,Renou, Christelle,Rowland, Scott,Sato, Yosuke,Shaw, Michael,Shen, Luhua,Shi, Zhan,Skene, Robert,Soucy, Francois,Stroud, Steve,Xu, He,Xu, Tianlin,Abu-Yousif, Adnan O.,Zhang, Ji
supporting information, p. 6902 - 6923 (2021/06/21)
Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route. Here, we describe the identification of STING agonist 15a, a cyclic dinucleotide structurally diversified from natural ligands with optimized properties for systemic intravenous (iv) administration. Our studies have shown that STING activation by 15a leads to an acute innate immune response as measured by cytokine secretion and adaptive immune response via activation of CD8+ cytotoxic T-cells, which ultimately provides robust antitumor efficacy.
High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
Bookser, Brett C.,Raffaele, Nicholas B.
, p. 173 - 179 (2007/10/03)
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
