112233-74-6Relevant articles and documents
Direct Prebiotic Pathway to DNA Nucleosides
Teichert, Jennifer S.,Kruse, Florian M.,Trapp, Oliver
, p. 9944 - 9947 (2019)
It is assumed that RNA played a key role in the origin of life, and the transition to more complex but more stable DNA for continuous information storage and replication requires the development of a ribonucleotide reductase to obtain the deoxyribonucleot
Synthesis of Lipophilic Guanine N-9 Derivatives: Membrane Anchoring of Nucleobases Tailored to Fatty Acid Vesicles
Wamberg, Michael C.,Pedersen, Pernille L.,L?ffler, Philipp M. G.,Albertsen, Anders N.,Maurer, Sarah E.,Nielsen, Kent A.,Monnard, Pierre-Alain
, p. 1893 - 1905 (2017)
Covalent or noncovalent surface functionalization of soft-matter structures is an important tool for tailoring their function and stability. Functionalized surfaces and nanoparticles have found numerous applications in drug delivery and diagnostics, and new functionalization chemistry is continuously being developed in the discipline of bottom-up systems chemistry. The association of polar functional molecules, e.g., molecular recognition agents, with soft-matter structures can be achieved by derivatization with alkyl chains, allowing noncovalent anchoring into amphiphilic membranes. We report the synthesis of five new guanine-N9 derivatives bearing alkyl chains with different attachment chemistries, exploiting a synthesis pathway that allows a flexible choice of hydrophobic anchor moiety. In this study, these guanine derivatives were functionalized with C10 chains for insertion into decanoic acid bilayer structures, in which both alkyl chain length and attachment chemistry determined their interaction with the membrane. Incubation of these guanine conjugates, as solids, with a decanoic acid vesicle suspension, showed that ether- and triazole-linked C10 anchors yielded an increased partitioning of the guanine derivative into the membranous phase compared to directly N-9-linked saturated alkyl anchors. Decanoic acid vesicle membranes could be loaded with up to 5.5 mol % guanine derivative, a 6-fold increase over previous limits. Thus, anchor chemistries exhibiting favorable interactions with a bilayer's hydrophilic surface can significantly increase the degree of structure functionalization.
Total Chemical Synthesis and Folding of All- l and All- d Variants of Oncogenic KRas(G12V)
Levinson, Adam M.,McGee, John H.,Roberts, Andrew G.,Creech, Gardner S.,Wang, Ting,Peterson, Michael T.,Hendrickson, Ronald C.,Verdine, Gregory L.,Danishefsky, Samuel J.
supporting information, p. 7632 - 7639 (2017/06/13)
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered "undruggable" due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-l- and all-d-amino acid biotinylated variants of oncogenic mutant KRas(G12V). The protein is synthesized using Fmoc-based solid-phase peptide synthesis and assembled using combined native chemical ligation and isonitrile-mediated activation strategies. We demonstrate that both KRas(G12V) enantiomers can successfully fold and bind nucleotide substrates and binding partners with observable enantiodiscrimination. By demonstrating the functional competency of a mirror-image form of KRas bound to its corresponding enantiomeric nucleotide triphosphate, this study sets the stage for further biochemical studies with this material. In particular, this protein will enable mirror-image yeast surface display experiments to identify all-d peptide ligands for oncogenic KRas, providing a useful tool in the search for new therapeutics against this challenging disease target.
New 7-methylguanine derivatives targeting the influenza polymerase PB2 cap-binding domain
Pautus, Stéphane,Sehr, Peter,Lewis, Joe,Fortuné, Antoine,Wolkerstorfer, Andrea,Szolar, Oliver,Guilligay, Delphine,Lunardi, Thomas,Décout, Jean-Luc,Cusack, Stephen
, p. 8915 - 8930 (2013/12/04)
The heterotrimeric influenza virus polymerase performs replication and transcription of viral RNA in the nucleus of infected cells. Transcription by "cap-snatching" requires that host-cell pre-mRNAs are bound via their 5′ cap to the PB2 subunit. Thus, the PB2 cap-binding site is potentially a good target for new antiviral drugs that will directly inhibit viral replication. Docking studies using the structure of the PB2 cap-binding domain suggested that 7-alkylguanine derivatives substituted at position N-9 and N-2 could be good candidates. Four series of 7,9-di- and 2,7,9-trialkyl guanine derivatives were synthesized and evaluated by an AlphaScreen assay in competition with a biotinylated cap analogue. Three synthesized compounds display potent in vitro activity with IC50 values lower than 10 μM. High-resolution X-ray structures of three inhibitors in complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and provide detailed information for further compound optimization.
Dynamers at the solid-liquid interface: Controlling the reversible assembly/reassembly process between two highly ordered supramolecular guanine motifs
Ciesielski, Artur,Lena, Stefano,Masiero, Stefano,Spada, Gian Piero,Samori, Paolo
supporting information; scheme or table, p. 1963 - 1966 (2010/06/21)
(Figure Presented) String quartet: A dynamic assembly/reassembly process in octadecyl guanine (G) monolayers was triggered by addition of [2.2.2]cryptand, potassium picrate (K+(pic)-), and trifluoromethanesulfonic acid. The resulting structures, which alternate between a hydrogen-bonded G ribbon and a G quartet, were monitored by STM at the solid-liquid interface on graphite (see picture).
Highly diastereoselective synthesis of modified nucleosides via an asymmetric multicomponent reaction
Ghosh, Arun K.,Kass, Jorden
scheme or table, p. 1218 - 1220 (2010/06/15)
We have developed a practical synthesis of unique nucleoside derivatives via TiCl4 promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation.
Positively-charged peptide nucleic acid analogs with improved properties
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Page/Page column 8-10, (2008/06/13)
The present invention relates to novel types of peptide nucleic acids (PNAS) with improved properties. In particular, it relates to positively charged PNA units having an ethylene linker between the backbone and the nucleobase, to oligonucleotide analogs comprising these units, to oligomers comprising these units, and to the use of positively charged PNAs as novel delivery agents with therapeutic and diagnostic applications including for antisense therapy.
Therapeutic and diagnostic ligand systems comprising transport molecule binding properties and medicaments containing the same
-
, (2008/06/13)
The invention relates to transport molecule binding ligand compounds which comprise a therapeutically and/or diagnostically active substance and a carrier molecule-affine substance with a high association constant to the carrier molecule. The invention also relates to medicaments containing these ligand compounds and to diagnostic kits.
Diastereoselective synthesis of N,O-psiconucleosides, a new class of modified nucleosides
Chiacchio, Ugo,Corsaro, Antonino,Pistara, Venerando,Rescifina, Antonio,Iannazzo, Daniela,Piperno, Anna,Romeo, Giovanni,Romeo, Roberto,Grassi, Giovanni
, p. 1206 - 1212 (2007/10/03)
Anomeric α- and β-N,O-psiconucleosides were prepared by 1,3-dipolar cycloaddition of C-ethoxycarbonyl N-methyl nitrone with ethyl 2-acetyloxyacrylate, followed by Vorbrueggen nucleosidation. The synthetic scheme has been applied to all purine and pyrimidine nucleobases. Nucleosidation can proceed under kinetic and under thermodynamic control; under thermodynamic control conditions only β-nucleosides are obtained for pyrimidine derivatives and α-nucleosides for purine derivatives. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
9-Vinylguanine: An easy access to aza-analogs of 2′,3′-dideoxyguanosine
Dalpozzo, Renato,De Nino, Antonio,Maiuolo, Loredana,Procopio, Antonio,De Munno, Giovanni,Sindona, Giovanni
, p. 4035 - 4038 (2007/10/03)
9-Vinylguanine, obtained for the first time and fully characterised by X-ray analysis, allows access to aza-analogues of 2′,3′-dideoxynucleosides through cycloaddition processes.
