18986-54-4Relevant academic research and scientific papers
Development of a p38α-selective radioactive probe for qualitative diagnosis of cancer using SPECT
Hirata, Masahiko,Yao, Tatsuma,Fujimura, Shigeaki,Kanai, Yasukazu,Yoshimoto, Mitsuyoshi,Sato, Takaji,Ohmomo, Yoshiro,Temma, Takashi
, p. 333 - 343 (2019/05/10)
Objective: p38 mitogen-activated protein (MAP) kinase (p38α) has drawn attention as a new target molecule for the treatment and diagnosis of cancer, and its overexpression and activation have been reported in various types of cancer. In this study, a single photon emission computed tomography (SPECT) imaging probe of p38α was developed to noninvasively image p38α activity for effective qualitative diagnosis of cancer. Methods: Pyrrolepyridine derivatives, m-YTM and p-YTM, were designed and synthesized based on the structure of the p38α-selective inhibitor. Radioactive iodine-labeled m-YTM, [125I]m-YTM, was synthesized because m-YTM greatly inhibited the phosphorylation of p38α upon examining the inhibitory effects of the compounds. After investigating the binding affinity of [125I]m-YTM to the recombinant p38α, a saturation binding experiment using activated p38α and inactive p38α was performed to determine the binding site. Uptake of [125I]m-YTM into various cancer cell lines was investigated, and the pharmacokinetics was evaluated using tumor-bearing mice. Results: The inhibitory activity of m-YTM was approximately 13 times higher than that of SB203580, a p38α-selective inhibitor. The binding site of [125I]m-YTM was estimated to be the p38α activating site, similar to that of SB203580, because the [125I]m-YTM bound strongly to both activated p38α and inactive p38α. Various different cancer cells incorporated [125I]m-YTM; however, its accumulation was significantly reduced by treatment with SB203580. Pharmacokinetics study of [125I]m-YTM in B-16 tumor-bearing mice was examined which revealed high accumulation of radioactivity in tumor tissues. The ratios of radioactivity in the B-16 tumor to that in blood were 3.1 and 50 after 1 and 24?h, respectively. The ratio of radioactivity in the tumor to that in blood in the tumor-bearing mice generated using other cancer cell lines was also ≥ 1 at 1?h after the administration of the probe. Conclusions: This study suggests that [123I]m-YTM has potential as a p38α imaging probe effective for various cancer types.
Glassy dynamics of hydrogen-bonded heteroditopic molecules
Lou, Nan,Wang, Yangyang,Li, Haixia,Sokolov, Alexei P.,Xiong, Huiming
, p. 4455 - 4460 (2012/11/13)
A self-complementary heteroditopic molecule composed of thymine and diamidopyridine end groups and a flexible aliphatic interconnecting chain has been synthesized. The glassy dynamics of this hydrogen-bonded supramolecule have been investigated by using dielectric and rheological measurements, in combination with infra-red spectroscopy and solid-state 13C NMR experiments. Decoupling of main dielectric relaxation from viscosity has been found in the vicinity of the glass transition and the temperature dependence of viscosity appears to be stronger than that of dielectric relaxation. The unusual dynamic decoupling phenomenon is ascribed to the chemical/dynamic heterogeneity and formation of hydrogen bonds in the supramolecules.
Towards a universal polymer backbone: Design and synthesis of polymeric scaffolds containing terminal hydrogen-bonding recognition motifs at each repeating unit
Stubbs, Ludger P.,Weck, Marcus
, p. 992 - 999 (2007/10/03)
Polymers containing terminal hydrogen-bonding recognition motifs based on diaminotriazine and diaminopyridine groups in their side chains for the self-assembly of appropriate receptors have been prepared by ring-opening metathesis polymerization (ROMP) of
Identification of sequence selective receptors for peptides with a carboxylic acid terminus
Braxmeier, Tobias,Demarcus, Mariangela,Fessmann, Thilo,McAteer, Stephen,Kilburn, Jeremy D.
, p. 1889 - 1898 (2007/10/03)
Split-and-mix libraries of resin-bound "tweezer" receptors have been prepared and screened to identify receptors for dye-labelled tripeptides. The receptors incorporate a diamidopyridine unit to serve as a specific recognition site for the CO2H
Identification of sequence-selective receptors for peptides with a carboxylic acid terminus
Fessmann, Thilo,Kilburn, Jeremy D.
, p. 1993 - 1996 (2007/10/03)
A combinatorial library of 'tweezer' receptors, which incorporate a diamidopyridine unit to provide a specific binding site for a CO2H group (see picture), can be screened to identify sequence-selective receptors for chosen peptide guests with
