78603-12-0Relevant articles and documents
The microenvironment and pKaperturbation of aminoacyl-tRNA guided the selection of cationic amino acids
Hazra, Bibhas,Prasad, Mahesh,Roy, Rajat,Tarafdar, Pradip K.
supporting information, p. 8049 - 8056 (2021/10/04)
The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and the terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino propionic acid (Dpr) with fewer methylene groups in the side chain remains an important question! The propensity of aminoacyl-tRNA (aa-tRNA) model substrates towards self-degradationviaintramolecular lactamization was studied using UV spectroscopy and1H-NMR titration, which showed that Lys and Arg remain stable, and Orn and Dab cyclize to lactam. Hydrophobicity-assisted surface mediated model peptide formation highlighted that the microenvironment and pKaperturbation led to poor regioselectivity (α-aminevs.terminal amine) in Dpr and other non-proteinogenic analogues. The α-selectivity became even poorer in the presence of phosphate, making them ill-suited for peptide synthesis. Superior regioselectivity of the Lys aa-tRNA model substrate suggests that the extra methylene bridge helped nature to separate the microenvironments of the α-amine and ε-amine to synthesize the peptide backbone.
N,N,N-Tris(tert-butoxycarbonyl)-l-arginine: five isoforms whose obtainment depends on procedure and scrupulous NMR confirmation of their structures
Alfei, Silvana,Castellaro, Sara
, p. 1811 - 1832 (2017/12/04)
l-arginine is often covalently linked to vectors for gene or drug delivery as a means of increasing their transfection activity and reducing toxicity. This strategy relies on the protection of basic nitrogen atoms, for example, by employing the tert-butoxycarbonyl group. Our aim in the present work was to prepare the widely described αN,ωN,ω′N-tris(tert-butyloxycarbonyl)-l-arginine as a single isomer in high yield and with high levels of purity for use in the esterification of dendrimers with several peripheral hydroxyl groups. Following three reported protocols which assured this goal, we observed the unexpected formation of four additional isomers. Using the first procedure, αN,ωN,ω′N-tris(tert-butyloxycarbonyl)-l-arginine was never obtained. The second procedure delivered the desired compound as a mixture of geometric isomers (E/Z), while the third protocol led to a single isomer in high yield and purity, but with an unreported symmetrical structure. Since Boc protection is transient, this discovery would seem to be of little interest, but preliminary results from an ongoing investigation of the behavior of each of the isomers obtained in the esterification reactions of interest has shown that their reactivity depends on their structure. Although this research is ongoing, here we report a detailed description of these unexpected results, along with an NMR investigation focusing on the double-bond geometry and position which enabled confirmation of the structures.
A study on effects of naphthalimide derivative-capped quantum dots on the cellular internalization, proliferation, and apoptosis ability
Zhao, Mei-Xia,Zeng, Er-Zao,Li, Yang,Wang, Chao-Jie
, p. 7351 - 7359 (2015/02/19)
Quantum dots (QDs) have shown great potential in monitoring and imaging cancer cells because of their unique photochemical and photophysical properties. However, it is little-known whether QDs affect the cellular internalization, proliferation and apoptosis. Here a new class of multifunctional QDs capped with ligands that possess l-Lys or l-Arg and naphthalimide (NI), linked by carboxyl groups (l-Lys-NI@QDs and l-Arg-NI@QDs, respectively), have been synthesized. We found that these QDs are of controllable sizes, in the range of 4 to 5 nm and have strong optical emission properties. The cellular uptake of NI derivative-capped QDs was monitored by flow cytometry and confocal microscopy. The results of in vitro cytotoxicity revealed that NI derivative-capped QDs, with better cell selectivity, could inhibit the growth of multiple cancer cells more potently than amonafide. They effectively inhibited the proliferation of cells due to apoptosis, which was confirmed by Hoechst 33342, annexin V-FITC and JC-1 staining and mitochondrial membrane potential (MMP) experiments. The most potent NI derivative-capped QDs, l-Arg-NI@CdSe/ZnS, were verified to efficiently induce apoptosis via a reactive oxygen species (ROS) mediating mitochondrial dysfunction, and were more effective in promoting programmed cell death in HepG2 cells in a preliminary mechanistic study. This journal is
