25021-08-3Relevant articles and documents
Advanced aqueous-phase phosphoramidation reactions for effectively synthesizing peptide-oligonucleotide conjugates trafficked into a human cell line
Wang, Tzu-Pin,Ko, Ni Chien,Su, Yu-Chih,Wang, Eng-Chi,Severance, Scott,Hwang, Chi-Ching,Shih, Ying Ting,Wu, Min Hui,Chen, Yen-Hsu
, p. 2417 - 2433 (2012)
Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat48-57 peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.
The stereodynamics of macrocyclic succinimide-thioethers
Lenz, Stefan,Horx, Philip,Geyer, Armin
, (2018)
Maleimide-thiol coupling is a popular bioconjugation strategy, but little is known about the stereoselectivity and the stereodynamics of the succinimide thioether formed in a biopolymer environment. We used thiol 1,4-addition for the macrocyclisation of 5 designed pentapeptides with the ringsize of hexapeptides because they incorporate the succinimide thioether (4-8). Both succinimide diastereomers are observed in the constrained macrocyclic rings in each case. In spite of the low diastereoselectivity of the macrocyclisation reaction, there is a significant influence of the amino acid environment on the epimerization rate of the succinimide. Its half life can be as short as several hours at room temperature when Gly is the amino acid following the succinimide (peptide 8). On the contrary, no epimerization is detectable even after several weeks in the case of d-Phe C-terminal to the succinimide in peptide 4. Already the small selection of examples shows how big the differences in epimerization rates can be and that the local environment has a significant influence. The variation of amino acids in the vicinity of the ligation site points the way towards the synthesis of bioconjugates which are obtained as stable and separable diastereomers.
A simple network of synthetic replicators can perform the logical or operation
Allen, Victoria C.,Robertson, Craig C.,Turega, Simon M.,Philp, Douglas
, p. 1920 - 1923 (2010)
Figure presented A small network of synthetic replicators is capable of responding to instructional inputs such that the output of the network is an excess of one of the replicators whenever the input contains either or both of the replicators, mirroring
Synthesis of functionalized copillar[4+1]arenes and rotaxane as heteromultivalent scaffolds
Chen, Wenzhang,Mohy Ei Dine, Tharwat,Vincent, Stéphane P.
supporting information, p. 492 - 495 (2021/01/25)
In this study, novel copillar[4+1]arenes were used as central heteromultivalent scaffolds via orthogonal couplings with a series of biologically relevant molecules such as carbohydrates, α-amino acids, biotin and phenylboronic acid. Further modifications by introducing maleimides or cyclooctyne groups provided molecular probes adapted to copper-free click chemistry. An octa-azidated fluorescent rotaxane bearing two distinct ligands was also generated in a fully controlled manner.
Heat stabilizer for PVC and synthesizing method of heat stabilizer
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Paragraph 0025, (2019/01/06)
The invention provides a novel metallic soap heat stabilizer. The novel metallic soap heat stabilizer structurally comprises maleimide groups, substituted amide groups, multi-ether groups and metal ions and can be used as the heat stabilizer in a PVC proc
