Correction to "Synthetic, Functional Thymidine-Derived Polydeoxyribonucleotide Analogues from a Six-Membered Cyclic Phosphoester".
Ontology highlight
ABSTRACT:
SUBMITTER: Tsao YT
PROVIDER: S-EPMC8154422 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:A grand challenge that crosses synthetic chemistry and biology is the scalable production of functional analogues of biomacromolecules. We have focused our attention on the use of deoxynucleoside building blocks bearing non-natural bases to develop a synthetic methodology that allows for the construction of high molecular weight deoxynucleotide polymers. Our six-membered cyclic phosphoester ring-opening polymerization strategy is demonstrated, herein, by an initial preparation of novel polyphosphoesters, comprised of butenyl-functionalized deoxyribonucleoside repeat units, connected via 3',5'-backbone linkages. A thymidine-derived bicyclic monomer, 3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate, was synthesized in two steps directly from thymidine, via butenylation and diastereoselective cyclization promoted by N,N-dimethyl-4-aminopyridine. Computational modeling of the six-membered 3',5'-cyclic phosphoester ring derived from deoxyribose indicated strain energies at least 5.4 kcal/mol higher than those of the six-membered monocyclic phosphoester, 2-ethoxy-1,3,2-dioxaphosphinane 2-oxide. These calculations supported the hypothesis that the strained 3',5'-cyclic monomer can promote ring-opening polymerization to afford the resulting poly(3',5'-cyclic 3-(3-butenyl) thymidine ethylphosphate)s with low dispersities (? < 1.10). This advanced design combines the merits of natural product-derived materials and functional, degradable polymers to provide a new platform for functional, synthetically derived polydeoxyribonucleotide-analogue materials.
| S-EPMC5451148 | biostudies-literature
Project description:The seven-membered cyclic potassium alumanyl species, [{SiNMes }AlK]2 [{SiNMes }={CH2 SiMe2 N(Mes)}2 ; Mes=2,4,6-Me3 C6 H2 ], which adopts a dimeric structure supported by flanking K-aryl interactions, has been isolated either by direct reduction of the iodide precursor, [{SiNMes }AlI], or in a stepwise manner via the intermediate dialumane, [{SiNMes }Al]2 . Although the intermediate dialumane has not been observed by reduction of a Dipp-substituted analogue (Dipp=2,6-i-Pr2 C6 H3 ), partial oxidation of the potassium alumanyl species, [{SiNDipp }AlK]2 , where {SiNDipp }={CH2 SiMe2 N(Dipp)}2 , provided the extremely encumbered dialumane [{SiNDipp }Al]2 . [{SiNDipp }AlK]2 reacts with toluene by reductive activation of a methyl C(sp3 )-H bond to provide the benzyl hydridoaluminate, [{SiNDipp }AlH(CH2 Ph)]K, and as a nucleophile with BPh3 and RN=C=NR (R=i-Pr, Cy) to yield the respective Al-B- and Al-C-bonded potassium aluminaborate and alumina-amidinate products. The dimeric structure of [{SiNDipp }AlK]2 can be disrupted by partial or complete sequestration of potassium. Equimolar reactions with 18-crown-6 result in the corresponding monomeric potassium alumanyl, [{SiNDipp }Al-K(18-cr-6)], which provides a rare example of a direct Al-K contact. In contrast, complete encapsulation of the potassium cation of [{SiNDipp }AlK]2 , either by an excess of 18-cr-6 or 2,2,2-cryptand, allows the respective isolation of bright orange charge-separated species comprising the 'free' [{SiNDipp }Al]- alumanyl anion. Density functional theory (DFT) calculations performed on this moiety indicate HOMO-LUMO energy gaps in the of order 200-250 kJ mol-1 .
| S-EPMC8596455 | biostudies-literature
Project description:Cidofovir (HPMPC, 1), a broad-spectrum antiviral agent, is currently used to treat AIDS-related human cytomegalovirus (HCMV) retinitis and has recognized therapeutic potential for orthopox virus infections, but is limited by its low oral bioavailability. Cyclic cidofovir (2) displays decreased nephrotoxicity compared to 1, while also exhibiting potent antiviral activity. Here we describe in detail the synthesis and evaluation as prodrugs of four cHPMPC dipeptide conjugates in which the free POH of 2 is esterified by the Ser side chain alcohol group of an X-L-Ser(OMe) dipeptide: 3 (X=L-Ala), 4 (X=L-Val), 5 (X=L-Leu), and 6 (X=L-Phe). Perfusion studies in the rat establish that the mesenteric permeability to 4 is more than 20-fold greater than to 1, and the bioavailability of 4 is increased 6-fold relative to 1 in an in vivo murine model. In gastrointestinal and liver homogenates, the cHPMPC prodrugs are rapidly hydrolyzed to 2. Prodrugs 3, 4, and 5 are nontoxic at 100 microM in HFF and KB cells and in cell-based plaque reduction assays had IC 50 values of 0.1-0.5 microM for HCMV and 10 microM for two orthopox viruses (vaccinia and cowpox). The enhanced transport properties of 3-6, conferred by incorporation of a biologically benign dipeptide moiety, and the facile cleavage of the Ser-O-P linkage suggest that these prodrugs represent a promising new approach to enhancing the bioavailability of 2.
| S-EPMC2629803 | biostudies-literature
Project description:The first synthesis, isolation, and characterization of permidin-2-ylidene complexes of Pd(II) is reported with entry resulting from either a direct reaction with isolable six-membered N-heterocyclic carbene or from the enetetramine, arising from dimerization of the carbene. Furthermore, a simplified method to prepare N,N'-disubstituted perimidinium bromide salts, precursors to 1,3-disubstituted perimidin-2-ylidene, was achieved using ammonium bromide as a source of weak acid. Through synthesis and nuclear magnetic resonance spectroscopic analysis of a carbene-phosphinidine adduct, an interrogation of the fundamental π-bonding ability of 1,3-diisopropylperimidin-2-ylidene revealed this interaction to be weak and of a similar order to unsaturated imidazol-2-ylidenes.
| S-EPMC6644826 | biostudies-literature
Project description:Two new crystal structures of eight- and ten-membered cyclic bis-anisyl-phosphono-thioyl disulfanes, namely 2,5-bis-(4-meth-oxy-phen-yl)-1,6,3,4,2?5,5?5-dioxadi-thiadi-phospho-cane-2,5-di-thione, C16H18O4P2S4, and 2,5-bis-(4-meth-oxy-phen-yl)-1,6,3,4,2?5,5?5-dioxadi-thia-diphosphecane-2,5-di-thione, C18H22O4P2S4, have been determined and compared to structures of the ferrocenyl analogues. The eight-membered rings have similar conformations (TBC) but the ten-membered macrocycles are differently puckered. Structural parameters of the relevant SPSSPS motif have been analysed and are discussed in detail. Compound 1 was refined as an inversion twin and 2 was refined as a two-component rotational twin.
| S-EPMC5956339 | biostudies-literature
Project description:Straightforward synthesis of cholesterol functionalized aliphatic N-substituted 8-membered cyclic carbonate (Chol-8m) monomer is reported. Well-defined poly(ethylene glycol) (PEG) diblock copolymers were readily accessed via organo catalytic ring opening polymerization. These polymers show promise as building blocks for self-assembled nanostructures and steric stabilizers for liposomes.
| S-EPMC7219653 | biostudies-literature
Project description:Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2'-deoxyuridine (EdU) and 5-Chloro-2'-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2'-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry.
| S-EPMC3923809 | biostudies-literature
Project description:Plasmodium falciparum thymidylate kinase (PfTMPK) is a key enzyme in pyrimidine nucleotide biosynthesis. 3-Trifluoromethyl-4-chloro-phenyl-urea-?-thymidine has been reported as an inhibitor of Mycobacterium tuberculosis TMPK (MtTMPK). Starting from this point, we designed, synthesized and evaluated a number of thymidine analogues as antimalarials. Both 5'-urea-?- and ?-thymidine derivatives were moderate inhibitors of PfTMPK and furthermore showed moderate inhibition of parasite growth. The structure of several enzyme-inhibitor complexes provides a basis for improved inhibitor design. However, we found that certain 5'-urea-?-thymidine analogues had antimalarial activity where inhibition of PfTMPK is not the major mode of action. Optimization of this series resulted in a compound with potent antimalarial activity (EC(50) = 28 nM; CC(50) = 29 ?M).
| S-EPMC3530961 | biostudies-literature
Project description:The synthesis of an unusual 1-metalla-2,3-cyclobutadiene complex [rac-(ebthi)Ti(Me3SiC3SiMe3)] (rac-ebthi = rac-1,2-ethylene-1,1'-bis(η5-tetrahydroindenyl)), a formal metallacyclic analogue of a non-existent four-membered 1,2-cyclobutadiene, is described. By variation of the cyclopentadienyl ligand of the titanocene precursor it was possible to stabilise this highly exotic compound which selectively reacts with ketones and aldehydes to yield enynes by oxygen transfer to titanium. Analysis of the bonding and electronic structure of the metallacycle shows that the complex is best described as an unusual antiferromagnetically coupled biradicaloid system, possessing a formal Ti(iii) centre coordinated with a monoanionic radical ligand.
| S-EPMC6540905 | biostudies-literature
Project description:Treatment of potassium salts of silole dianions with donor stabilised germanium dichlorides gave the anticipated silagermafulvenylidenes R2Si = Ge(Do) (R2Si = 1-silacyclopentadiendiyl, Do = N-heterocyclic carbene (NHC)) only as transient intermediates in a side reaction. They were detected by NMR spectroscopy and, in one case, the formal dimer, 2,4-disila-1λ3,3λ3-digermetane, was isolated. The main products of these reactions are sila-bis-λ3-germiranes, i.e. directly interconnected digermylenes that are part of a three-membered ring. The structural data, supported by the results of density functional calculations confirm the digermylene nature of these products with a long inner cyclic Ge-Ge bond that decreases the inherent high ring strain in silagermiranes.
| S-EPMC8115106 | biostudies-literature