Search results for "Analogs"
showing 10 items of 53 documents
Synthetic mRNAs with Superior Translation and Stability Properties
2012
The translational efficiency and stability of synthetic mRNA in both cultured cells and whole animals can be improved by incorporation of modified cap structures at the 5'-end. mRNAs are synthesized in vitro by a phage RNA polymerase transcribing a plasmid containing the mRNA sequence in the presence of all four NTPs plus a cap dinucleotide. Modifications in the cap dinucleotide at the 2'- or 3'-positions of m(7)Guo, or modifications in the polyphosphate chain, can improve both translational efficiency and stability of the mRNA, thereby increasing the amount and duration of protein expression. In the context of RNA-based immunotherapy, the latter is especially important for antigen producti…
Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune r…
2010
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-c…
Inhibition of Cancer Derived Cell Lines Proliferation by Synthesized Hydroxylated Stilbenes and New Ferrocenyl-Stilbene Analogs. Comparison with Resv…
2014
Further advances in understanding the mechanism of action of resveratrol and its application require new analogs to identify the structural determinants for the cell proliferation inhibition potency. Therefore, we synthesized new trans-resveratrol derivatives by using the Wittig and Heck methods, thus modifying the hydroxylation and methoxylation patterns of the parent molecule. Moreover, we also synthesized new ferrocenylstilbene analogs by using an original protective group in the Wittig procedure. By performing cell proliferation assays we observed that the resveratrol derivatives show inhibition on the human colorectal tumor SW480 cell line. On the other hand, cell viability/cytotoxicit…
N-Benzyl Residues as the P1′ Substituents in Phosphorus-Containing Extended Transition State Analog Inhibitors of Metalloaminopeptidases
2020
Peptidyl enzyme inhibitors containing an internal aminomethylphosphinic bond system (P(O)(OH)-CH2-NH) can be termed extended transition state analogs by similarity to the corresponding phosphonamidates (P(O)(OH)-NH). Phosphonamidate pseudopeptides are broadly recognized as competitive mechanism-based inhibitors of metalloenzymes, mainly hydrolases. Their practical use is, however, limited by hydrolytic instability, which is particularly restricting for dipeptide analogs. Extension of phosphonamidates by addition of the methylene group produces a P-C-N system fully resistant in water conditions. In the current work, we present a versatile synthetic approach to such modified dipeptides, based…
Symmetric Fluoroborate and its Boron Modification: Crystal and Electronic Structures
2019
Four boron-carrying molecules were synthesized and purified. These were found to be (a) relatively neutral with respect to the parent BF derivative and (b) functionalized by donor&ndash
New 1,2,4-oxadiazole nortopsentin derivatives with cytotoxic activity
2019
New analogs of nortopsentin, a natural 2,4-bis(3&prime
Biological evaluation of new 1,2,4-oxadiazole topsentin analogs as anticancer agents
2019
Synthesis of novel 1,2,4-oxadiazole topsentin analogs with antitumor activity
2019
Synthesis of novel 1,2,4-oxadiazole topsentin analogs with antitumor activity
New Topsentin analogs as inhibitors of biofilm formation
Synthesis of methyl derivatives of linear and angular thienocoumarins and thiopyranocoumarins
1998
New linear and angular thienocoumarins and thiopyranocoumarins were synthesized. The key intermediates were appropriate methyl derivatives of 7-mercaptocoumarin, which were condensed with chloro-ketones or propargyl chloride. Thioethers were cyclized under various conditions in order to determine which methods produced the best yields of the desired thienocoumarins 15, 16, 17, 18, 22, 23, 24, 27 and thiopyranocoumarins 28 and 29.