• MeSH
• kouření MeSH
• manuály jako téma MeSH
• prevence kouření MeSH
• programy národního zdraví MeSH
• tabák MeSH
• tabákový průmysl MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• adiktologie
• NLK Publikační typ
• publikace WHO

Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent reactions or other chemistries, aiding in the creation of a variety of complex, drug-like molecules. These innovative tetrazole building blocks are efficiently and directly synthesized using a Passerini three-component reaction (PT-3CR), employing cost-effective and readily available materials. We further showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes. It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakty MeSH

Enantioselective approaches to the construction of four complex building blocks of the structurally intricate marine macrolide known as spongistatin 1 are presented. The first phase of the synthetic effort relies on a practical approach to a desymmetrized, enantiomerically pure spiroketal ring system incorporating rings A and B. Concurrently, the C17–C28 subunit, which houses one-fifth of the stereogenic centers of the target in the form of rings C and D, was assembled via a composite of stereocontrolled aldol condensations. Once arrival at the entire C1–C28 sector had been realized, routes were devised to provide two additional highly functionalized sectors consisting of C29–C44 and C38–C51. A series of subsequent transformations including cyclization of the E ring and hydroboration to afford the B-alkyl intermediate for the key Suzuki coupling to append the side chain took advantage of efficient stereocontrol. Ultimately, complete assembly and functionalization of the western EF sector of spongistatin was thwarted by an inoperative Suzuki coupling step intended to join the side chain to the C29–C44 sector, and later because of complications due to protecting groups, which precluded the complete elaboration of the late stage C29–C51 intermediate.

• MeSH
• antimitotika chemická syntéza   MeSH
• makrolidy chemická syntéza   MeSH
• modulátory tubulinu chemická syntéza   MeSH

2'-Deoxyribonucleoside triphosphates (dNTPs) containing 5-(hydroxymethyl)cytosine (5hmC) protected with photocleavable groups (2-nitrobenzyl or 6-nitropiperonyl) were prepared and studied as substrates for the enzymatic synthesis of oligonucleotides and DNA containing a photocaged epigenetic 5hmC base. DNA probes containing photocaged or free 5hmC in the recognition sequence of restriction endonucleases were prepared and used for the study of the photorelease of caged DNA by UV or visible light at different wavelengths. The nitrobenzyl-protected dNTP was a slightly better substrate for DNA polymerases in primer extension or PCR, whereas the nitropiperonyl-protected nucleotide underwent slightly faster photorelease at 400 nm. However, both photocaged building blocks can be used in polymerase synthesis and the photorelease of 5hmC in DNA.

• MeSH
• 5-methylcytosin analogy a deriváty   chemická syntéza   chemie   MeSH
• deoxyribonukleosidy chemická syntéza   chemie   MeSH
• DNA chemická syntéza   chemie   MeSH
• fotochemické procesy MeSH
• polyfosfáty chemická syntéza   chemie   MeSH
• světlo MeSH
• ultrafialové záření MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Explicit solvent molecular dynamics (MD) was used to describe the intrinsic flexibility of the helix 42-44 portion of the 23S rRNA (abbreviated as Kt-42+rGAC; kink-turn 42 and GTPase-associated center rRNA). The bottom part of this molecule consists of alternating rigid and flexible segments. The first flexible segment (Hinge1) is the highly anharmonic kink of Kt-42. The second one (Hinge2) is localized at the junction between helix 42 and helices 43/44. The rigid segments are the two arms of helix 42 flanking the kink. The whole molecule ends up with compact helices 43/44 (Head) which appear to be modestly compressed towards the subunit in the Haloarcula marismortui X-ray structure. Overall, the helix 42-44 rRNA is constructed as a sophisticated intrinsically flexible anisotropic molecular limb. The leading flexibility modes include bending at the hinges and twisting. The Head shows visible internal conformational plasticity, stemming from an intricate set of base pairing patterns including dynamical triads and tetrads. In summary, we demonstrate how rRNA building blocks with contrasting intrinsic flexibilities can form larger architectures with highly specific patterns of preferred low-energy motions and geometries.

• MeSH
• archeální RNA chemie   MeSH
• financování organizované MeSH
• Haloarcula marismortui genetika   MeSH
• ionty chemie   MeSH
• konformace nukleové kyseliny MeSH
• konzervovaná sekvence MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• párování bází MeSH
• počítačová simulace MeSH
• pohyb těles MeSH
• RNA ribozomální 23S chemie   MeSH
• sekvence nukleotidů MeSH

• MeSH
• acetaldehyd chemická syntéza   MeSH
• aminokyseliny chemie   MeSH
• dipeptidy chemická syntéza   chemie   MeSH
• Diptera MeSH
• finanční podpora výzkumu jako téma MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Among lizards, only monitor lizards (Varanidae) have a functionally divided cardiac ventricle. The division results from the combined function of three partial septa, which may be homologous to the ventricular septum of mammals and archosaurs. We show in developing monitors that two septa, the 'muscular ridge' and 'bulbuslamelle', express the evolutionarily conserved transcription factors Tbx5, Irx1 and Irx2, orthologues of which mark the mammalian ventricular septum. Compaction of embryonic trabeculae contributes to the formation of these septa. The septa are positioned, however, to the right of the atrioventricular junction and they do not participate in the separation of incoming atrial blood streams. That separation is accomplished by the 'vertical septum', which expresses Tbx3 and Tbx5 and orchestrates the formation of the electrical conduction axis embedded in the ventricular septum. These expression patterns are more pronounced in monitors than in other lizards, and are associated with a deep electrical activation near the vertical septum, in contrast to the primitive base-to-apex activation of other lizards. We conclude that evolutionarily conserved transcriptional programmes may underlie the formation of the ventricular septa of monitors.

• MeSH
• časosběrné zobrazování MeSH
• echokardiografie veterinární   MeSH
• embryo nesavčí MeSH
• homeodoménové proteiny genetika   fyziologie   MeSH
• ještěři embryologie   genetika   MeSH
• mezikomorová přepážka diagnostické zobrazování   embryologie   MeSH
• molekulární evoluce MeSH
• proteiny T-boxu genetika   fyziologie   MeSH
• srdeční komory diagnostické zobrazování   embryologie   MeSH
• srdeční síně diagnostické zobrazování   embryologie   MeSH
• těžké řetězce myosinu genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

Dinucleoside polyphosphates (NpnNs) were discovered 50 years ago in all cells. They are often called alarmones, even though the molecular target of the alarm has not yet been identified. Recently, we showed that they serve as noncanonical initiating nucleotides (NCINs) and fulfill the role of 5' RNA caps in Escherichia coli. Here, we present molecular insight into their ability to be used as NCINs by T7 RNA polymerase in the initiation phase of transcription. In general, we observed NpnNs to be equally good substrates as canonical nucleotides for T7 RNA polymerase. Surprisingly, the incorporation of ApnGs boosts the production of RNA 10-fold. This behavior is due to the pairing ability of both purine moieties with the -1 and +1 positions of the antisense DNA strand. Molecular dynamic simulations revealed noncanonical pairing of adenosine with the thymine of the DNA.

• MeSH
• bakteriofág T7 enzymologie   MeSH
• dinukleosidfosfáty genetika   metabolismus   MeSH
• DNA řízené RNA-polymerasy genetika   metabolismus   MeSH
• DNA metabolismus   MeSH
• iniciace genetické transkripce * MeSH
• párování bází MeSH
• RNA čepičky genetika   MeSH
• RNA genetika   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• vazba proteinů MeSH
• virové proteiny genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH