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61.
Design, synthesis, and binding affinities of pyrrolinone-based somatostatin mimetics 总被引:1,自引:0,他引:1
Smith AB Charnley AK Mesaros EF Kikuchi O Wang W Benowitz A Chu CL Feng JJ Chen KH Lin A Cheng FC Taylor L Hirschmann R 《Organic letters》2005,7(3):399-402
[structure: see text] Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (D,L-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporating the requisite functionalized coded and noncoded amino acid side chains, comprised a longest linear synthetic sequence of 23 steps. Binding affinities at two somatostatin receptor subtypes (hsst 4 and 5) reveal micromolar activity, demonstrating that the d,l-mixed pyrrolinone scaffold can be employed to generate functional mimetics of peptide beta-turns. 相似文献
62.
Sajal Sen Mark W. Perrin Adam C. Sedgwick Vincent M. Lynch Jonathan L. Sessler Jonathan F. Arambula 《Chemical science》2021,12(21):7547
Recent decades have witnessed the emergence of Au(i) bis-N-heterocyclic carbenes (NHCs) as potential anticancer agents. However, these systems exhibit little interaction with serum proteins (e.g., human serum albumin), which presumably impacts their pharmacokinetic profile and tumor exposure. Anticancer drugs bound to human serum albumin (HSA) often benefit from significant advantages, including longer circulatory half-lives, tumor targeted delivery, and easier administration relative to the drug alone. In this work, we present Au(i) bis-NHCs complexes, 7 and 9, capable of binding to HSA. Complex 7 contains a reactive maleimide moiety for covalent protein conjugation, whereas its congener 9 contains a naphthalimide fluorophore for non-covalent binding. A similar drug motif was used in both cases. Complexes 7 and 9 were prepared from a carboxylic acid functionalized Au(i) bis-NHC (complex 2) using a newly developed post-synthetic amide functionalization protocol that allows coupling to both aliphatic and aromatic amines. Analytical, and in vitro techniques were used to confirm protein binding, as well as cellular uptake and antiproliferative activity in A549 human lung cancer cells. The present findings highlight a hitherto unexplored approach to modifying Au(i) bis-NHC drug candidates for protein ligation and serve to showcase the relative benefits of covalent and non-covalent HSA binding.Au(i) bis-N-heterocyclic carbenes (NHCs) functionalized using an amide linker were found to bind to human serum albumin (HSA) in covalent and non-covalent fashion. The solubility and in vitro anti-cancer activity of these new conjugates were studied. 相似文献
63.
Alicja Wawrzynów Adam Liwo Ewa Kaczmarczyk Lech Chmurzyński 《Journal of solution chemistry》1998,27(5):463-472
Cationic heteroconjugation equilibria of more than ninety systems consisting of substituted pyridines, their N-oxides, and trimethylamine N-oxide, i. e., in systems with mixed hydrogen bridges of type OHN+ (NHO+) were studied in propylene carbonate. Both experimental systems without proton transfer, BH+/B1, and those with proton transfer, B1H+/B, were explored. The stability of the mixed hydrogen bridges, OHN+ (NHO+), is compared with that of the OHC+-type bridges. The influence of the difference in basicity of the conjugate base of the proton donor and the proton acceptor on the presence of the proton transfer equilibria, and, consequently, the possibility of determination of the cationic heteroconjugation constant values is discussed. 相似文献
64.
The Ramanujan Journal - For two varieties of dimension 5 constructed as double covers of $$\mathbb {P}^5$$ branched along the union of 12 hyperplanes, we prove that the number of points... 相似文献
65.
The single machine group scheduling problem is considered. Jobs are classified into several groups on the basis of group technology, i.e. jobs of the same group have to be processed jointly. A machine set-up time independent of the group sequence is needed between each two consecutive groups. A schedule specifies the sequence of groups and the sequence of jobs in each group. The quality of a schedule is measured by the criteriaF
1, ...,F
m ordered by their relative importance. The objective is to minimize the least important criterionF
m subject to the schedule being optimal with respect to the more important criterionF
m–1 which is minimized on the set of schedules minimizing criterionF
m–2 and so on. The most important criterion isF
1, which is minimized on the set of all feasible schedules. An approach to solve this multicriterion problem in polynomial time is presented if functionsF
1, ...,F
m have special properties. The total weighted completion time and the total weighted exponential time are the examples of functionsF
1, ...,F
m–1 and the maximum cost is an example of functionF
m for which our approach can be applied.The research of the authors was partially supported by a KBN Grant No. 3 P 406 003 05, the Fundamental Research Fund of Belarus, Project N 60-242, and the Deutsche Forschungsgemeinschaft, Project Schema, respectively. The paper was completed while the first author was visiting the University of Melbourne. 相似文献
66.
Abachi S Abbott B Abolins M Acharya BS Adam I Adams DL Adams M Ahn S Aihara H Alitti J Álvarez G Alves GA Amidi E Amos N Anderson EW Aronson SH Astur R Avery RE Baden A Balamurali V Balderston J Baldin B Bantly J Bartlett JF Bazizi K Bendich J Beri SB Bertram I Bezzubov VA Bhat PC Bhatnagar V Bhattacharjee M Bischoff A Biswas N Blazey G Blessing S Boehnlein A Bojko NI Borcherding F Borders J Boswell C Brandt A Brock R Bross A Buchholz D Burtovoi VS Butler JM Casey D Castilla-Valdez H 《Physical review letters》1995,75(6):1023-1027
67.
Abachi S Abbott B Abolins M Acharya BS Adam I Adams DL Adams M Ahn S Aihara H Alitti J Álvarez G Alves GA Amidi E Amos N Anderson EW Aronson SH Astur R Avery RE Baden A Balamurali V Balderston J Baldin B Bantly J Bartlett JF Bazizi K Bendich J Beri SB Bertram I Bezzubov VA Bhat PC Bhatnagar V Bhattacharjee M Bischoff A Biswas N Blazey G Blessing S Bloom P Boehnlein A Bojko NI Borcherding F Borders J Boswell C Brandt A Brock R Bross A Buchholz D Burtovoi VS Butler JM Casey D Castilla-Valdez H 《Physical review letters》1995,75(8):1456-1461
68.
Abachi S Abbott B Abolins M Acharya BS Adam I Adams DL Adams M Ahn S Aihara H Alitti J Álvarez G Alves GA Amidi E Amos N Anderson EW Aronson SH Astur R Avery RE Baden A Balamurali V Balderston J Baldin B Bantly J Bartlett JF Bazizi K Bendich J Beri SB Bertram I Bezzubov VA Bhat PC Bhatnagar V Bhattacharjee M Bischoff A Biswas N Blazey G Blessing S Boehnlein A Bojko NI Borcherding F Borders J Boswell C Brandt A Brock R Bross A Buchholz D Burtovoi VS Butler JM Casey D Castilla-Valdez H 《Physical review letters》1995,75(4):618-623
69.
P. Abreu W. Adam E. Agasi I. Ajinenko R. Aleksan G. D. Alekseev P. P. Allport S. Almehed F. M. L. Almeida S. J. Alvsvaag et al. 《Zeitschrift fur Physik C Particles and Fields》1995,66(3):341-354
The forward-backward asymmetries for the processes
and
at theZ resonance are measured using identifiedD
*± mesons. In 905,000 selected hadronic events, taken in 1991 and 1992 with the DEL-PHI detector at LEP, 4757D
*+D
0+ decays are reconstructed. Thec andb quark forward-backward asymmetries are determined to be:
相似文献
70.
P. Abreu W. Adam T. Adye E. Agasi I. Ajinenko R. Aleksan G. D. Alekseev P. P. Allport S. Almehed S. J. Alvsvaag et al. 《Zeitschrift fur Physik C Particles and Fields》1995,68(3):353-362
The decayB
*B
has been observed with the DELPHI detector at LEP, where theB
* meson is produced inZ boson decays. The combination of inclusively reconstructedB mesons with well-measured converted photons yields a measurement of the flavour-averagedB
*-B mass difference of 45.5±0.3 (stat.) ±0.8 (syst.) MeV/c2. 95% confidence level upper limits at 6 MeV/c2 are placed on both the isospin (i.e.B
+-B
0) and theB
s
-B
ud
splitting of the mass difference. The production ratio ofB
* toB mesons inZ decays is measured to be 0.72±0.03 (stat.) ±0.06 (syst.). Limits on the production cross-section of other hypothetical excitedB hadron states decaying radiatively are established. The differentialB
* cross section has been measured to be in good agreement with the averageb fragmentation, yielding an average fractionalB
* energy of x
E
=0.695±0.009 (stat.) ±0.013 (syst.). From the decay angular distribution the relative contribution of longitudinalB
* polarisation states is measured to be L/(L + T) = 0.32 ± 0.04 (stat.) ±0.03 (syst.).CICYT_AEN93-0832 相似文献
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