2620-09-9Relevant articles and documents
Preclinical evaluation of DO3P-AME-DO3P: A polyazamacrocyclic methylene phosphonate for diagnosis and therapy of skeletal metastases
Tanwar, Jyoti,Datta, Anupama,Tiwari, Anjani Kumar,Thirumal, Meganathan,Chuttani, Krishna,Mishra, Anil Kumar
, p. 244 - 255 (2011)
A phosphonate derivative 10′-bis(acetamido)-ethane-bis[1,4,7- tri(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane] (DO3P-AME-DO3P), was synthesized with 90% yield in high purity. It was labeled with 99mTc in 97.5% efficiency and specific activity of 112-250 MBq/μmol. The binding affinity of 99mTc-DO3P-AME-DO3P towards bone minerals was tested in vitro by using hydroxy apatite as a bone model with absorption of 93% during the first hour of the experiment. Receptor binding assay on human bone cell line SAOS-2 demonstrated Kd value of 1.07 nM. Cell binding studies of DO3P-AME-DO3P on osteoblasts and osteoclasts cells performed in vitro displayed preferential affinity of the compound towards osteoclast (167.95 ± 3.56% dose/mg protein). The serum stability of 99mTc complex was found to be 96.8% after 24 h. Blood kinetics of 99mTc-DO3P-AME-DO3P performed on normal rabbits showed fast clearance with t1/2(F) = 15 min ± 0.014 min and t1/2(S) = 4 h 3 min ± 0.09 min. Biodistribution studies carried out in normal BALB/c mice showed bone-to-blood ratio of 20 and bone-to-muscle ratio of 33. The bone tissue demonstrated highest concentration of bound radioactivity with 10.73% ID/g at 1 h post injection. The protonation and stability constants were determined by pH-potentiometry titrations. The stability constants of DO3P-AME-DO3P with Lu(III), Sm(III), and Ho(III) were 19.7, 21.8, and 20.2 determined by "out of cell" method. The excellent bone seeking properties of DO3P-AME-DO3P make it a candidate of choice for SPECT imaging and preferential uptake of the compound in osteoclasts in comparison to osteoblasts; BMM and BMC can be used to understand the pathway of pathogenesis of osteoporosis and skeletal metastases.
Goto et al.
, p. 1488,1489 (1970)
A "turn-on" fluorescent sensor for cytosine in aqueous media based on diamino-bridged biphenyl acrylonitrile
Chen, Jiaojiao,Zhou, Bangyi,Li, Yongsheng,Zheng, Linlu,Guo, Hongyu,Yang, Fafu
, p. 1373 - 1380 (2021)
The detection of cytosine is of significance for analyzing DNA bases, but no "turn-on"fluorescent sensor for cytosine in aqueous media has been reported so far. In this study, series of diamino-bridged biphenyl acrylonitriles 3a-3c were designed and synthesized with yields of 70-75%. The sensing experiments for 16 types of ions and biomolecules suggested that compound 3b with butanediamino bridges exhibited good selective sensing abilities towards cytosine based on "turn-on"fluorescence enhancement. The detection limit of compound 3b for cytosine attained 1.02 × 10-7 M. The selective sensing ability towards cytosine was little influenced by other species and remained stable between pH = 6-9. The sensing mechanism was proposed by the analysis of Job's plot, 1H NMR and MS binding spectra. The sensing ability for cytosine was successfully used for analysing urine samples with the recovery over 94%. Sample 3b also exhibited good bioimaging performance with bright blue-green fluorescence for sensing cytosine, implying the application prospect in complicated and living environment.
In Situ Cyclization of Native Proteins: Structure-Based Design of a Bicyclic Enzyme
Pelay-Gimeno, Marta,Bange, Tanja,Hennig, Sven,Grossmann, Tom N.
supporting information, p. 11164 - 11170 (2018/08/28)
Increased tolerance of enzymes towards thermal and chemical stress is required for many applications and can be achieved by macrocyclization of the enzyme resulting in the stabilizing of its tertiary structure. Thus far, macrocyclization approaches utilize a very limited structural diversity, which complicates the design process. Herein, we report an approach that enables cyclization through the installation of modular crosslinks into native proteins composed entirely of proteinogenic amino acids. Our stabilization procedure involves the introduction of three surface-exposed cysteine residues, which are reacted with a triselectrophile, resulting in the in situ cyclization of the protein (INCYPRO). A bicyclic version of sortase A was designed that exhibits increased tolerance towards thermal as well as chemical denaturation, and proved to be efficient in protein labeling under denaturing conditions. In addition, we applied INCYPRO to the KIX domain, resulting in up to 24 °C increased thermal stability.
