10.1002/chem.201902411
The research focuses on the chemical synthesis of an oligoribonucleotide (ASL of tRNALys T. brucei) that contains a recently discovered cyclic form of 2-methylthio-N6-threonylcarbamoyladenosine (ms2ct6A). The team developed a method for synthesizing the protected form of ms2t6A from adenosine or guanosine using an optimized carbamate method and, for the first time, the isocyanate route. They then transformed the hypermodified nucleoside into a protected ms2t6A-phosphoramidite monomer, which was used to synthesize a 17-nucleotide precursor oligonucleotide. The key experiment involved a stereochemically secure cyclization of ms2t6A to ms2ct6A at the oligonucleotide level, yielding an oligonucleotide bearing the ms2ct6A unit. The synthesized oligonucleotides were analyzed using techniques such as RP-HPLC, MALDI-TOF MS, and nucleoside composition analysis to confirm their structures and purities. This research provides a method for producing oligonucleotides suitable for studying the structure-activity relationships of tRNA modifications.
10.1021/jo902190c
The research focuses on the synthesis and crystal structure analysis of a selenium-modified nucleic acid, specifically 20-Se-modified guanosine (GSe) incorporated into DNA. The study describes a convenient synthesis method for the 20-SeMe-modified guanosine phosphoramidite, a new building block for DNA and RNA derivatization, and reports on the first incorporation of the 2-Se-G moiety into DNA. The X-ray crystal structure of the 20-Se-modified octamer DNA (50-GTGSeTACAC-30) was determined at a resolution of 1.20 ?, revealing that the 20-Se modification points to the minor groove and causes no significant structure perturbation compared to the native DNA. The experiments involved protecting hydroxyl groups of guanosine with TIPDS, acylating the guanosine amino group with isobutyryl group, and introducing a selenium atom through a series of reactions including silylation, selective deprotection, and treatment with sodium methylselenide. The synthesized phosphoramidite was then used to incorporate the 2-Se-G modification into DNA. The study utilized various analytical techniques such as NMR spectroscopy, mass spectrometry, and high-performance liquid chromatography (HPLC) for compound characterization and purification. The crystallization behavior of the modified DNA was screened using the Hampton kit, and X-ray diffraction data collection was performed at the NSLS beamline. The structure determination and refinement were carried out using molecular replacement and a series of computational methods.
10.1002/hlca.201300043
The research focuses on the synthesis and characterization of oligonucleotide analogues with integrated bases and backbone (ONIBs), specifically targeting the self-complementary thiomethylene-linked octanucleoside. The purpose of this investigation is to demonstrate that the structural differentiation of oligonucleotides into a contiguous backbone and appended nucleobases is not a prerequisite for pairing or the formation of defined conformers. The research aims to create ONIBs that can pair in aqueous solutions, challenging the traditional structure of nucleic acids. Key chemicals used in the synthesis process include various nucleoside derivatives, such as guanosine, cytidine, and uridine, along with protecting groups like methoxytrityl (MMTr) and isopropylidene groups. The conclusions drawn from the study indicate that the pairing properties of these analogues are influenced by the sequence of nucleobases and the constitution and conformation of the linking elements. The study successfully synthesized and analyzed the structures of the target octanucleosides, revealing that the fully deprotected octanucleoside forms a duplex with complete base pairing, while the partially protected version forms a mixture of associated species with at most four Watson-Crick base pairs.
10.1021/jm00121a016
The study primarily focuses on the synthesis and evaluation of various nucleoside analogues as potential anti-HIV agents. The researchers synthesized a series of 1',2'-seco-dideoxynucleosides, including cytidine (12), guanosine (14), adenosine (16), and inosine (18) analogues, starting from (R)-benzylglycidol. These compounds were prepared through a series of chemical reactions involving epoxidation, alkylation, and debenzylations. The synthesized compounds were then tested for their antiviral activity against HIV-1 in ATH8 cells and their cytotoxicity in uninfected human PBM cells. Additionally, the study also evaluated the compounds for activity against HSV-1 and HSV-2 using plaque reduction assays in Vero cells. The results indicated that these nucleoside analogues did not show significant antiviral activity against HIV-1 compared to the reference compound ddAdo. The study provides insights into the chemical synthesis of these nucleoside analogues and their potential as antiviral agents, highlighting the importance of further research to optimize their structures for enhanced activity.
10.1021/jm00047a014
The research focuses on the synthesis and activity of 7,8-disubstituted guanosines and related compounds as potential immunostimulants. The purpose of this study was to design and prepare a series of these derivatives to act as B-cell selective activators of the humoral immune response, evaluating their ability to act as B-cell mitogens, augment antibody responses, and stimulate natural killer (NK) cell responses. The research concluded that certain compounds, particularly those with a medium-length alkyl chain on the 7-position of 7-alkyl-8-oxoguanosines, demonstrated potent in vivo activity when administered intravenously, subcutaneously, or orally. Notably, 7-allyl-8-oxoguanosine (loxoribine, RWJ-21757) was identified as the most potent and was chosen for further development due to its overall biological profile and ease of synthesis. The study involved a variety of chemicals, including guanosine derivatives, alkyl and benzyl electrophiles, and various reagents used in the synthesis and purification processes, such as sodium hydride, epibromohydrin, and different protecting groups for the nucleosides.
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