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彭师奇, Caixia Huo, † Chao Wang, † Ming Zhao, † and Shiqi Peng*, ‡
Chem. Res. Toxicol. 2004, 17, 1112-1120,-0001,():
-1年11月30日
N-(1-Deoxy-D-fructos-1-yl)-L-amino acids isolated from hog liver are endogenous lead decorporation substances with low toxicity and cell membrane crossing ability. To simulate the effect of the natural N-(1-deoxy-D-fructos-1-yl)-L-amino acids on lead decorporation, a ser ies of the epimerically pure N-(1-deoxy-D-fructos-1-yl)-L-amino acids (6a-eβ) were synthesized, and their usefulness as antagonists of lead intoxication was investigated. The results suggest that after treatment with 6a-eβ the liver, kidney, bone, and brain, lead levels of mice were significantly reduced in comparison with the control group. Except for bone and brain lead levels of the mice after chelating treatment with 6dβ, all of the other tissue lead levels of mice after chelating treatment with 6a-eβ are significantly lower than those of mice after treatment with DL-penicillamine (p<0.05). All fecal lead levels of mice after treatment with 6a-eβ are significantly higher than those of mice after treatment with 0.9% saline (controls) and DLpenicillamine (p<0.05-0.01). The effects of all chelating agents on urinary excretion of lead in mice are clearly superior to the control (p<0.05-0.01). The results of the present studies on repeated lead exposure indicated that at tested levels of i.p. injections, the fructose-amino acids were effective antagonists of lead poisoning under the experimental conditions. After treatment with the chelators, the concentration of essential metals in mice did not exhibit change as compared to the control. The effects of the compounds on cadmium decorporation were also investigated, and similar results were observed.
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【期刊论文】Synthesis and Thrombolytic Activity of Fibrinogen Fragment Related Cyclopeptides
彭师奇, Ming Zhao, Na Lin, Chao Wang and Shiqi Peng*
Bioorganic & Medicinal Chemistry Letters 13(2003)961-964,-0001,():
-1年11月30日
In the modification of the fibrinogen fragment related sequences ARPAK, QRPAK GRPAK and KRPAK, the corresponding cyclo-ARPAK, cyclo-QRPAK, cyclo-GRPAK, and cyclo-KRPAK were prepared in the diluted solution. The bioassay in vivo indicated that the thrombolytic potencies of cyclo-ARPAK, cyclo-GRPAK, cyclo-QRPAK, and cyclo-KRPAK were significantly higher than that of ARPAK, QRPAK, GRPAK, and KRPAK. In water, the cyclopeptides were incubated with pepsin or trypsin at 37 C for 64h. There was no degradation product observed, on the other hand, with the same condition, the peptides were completely hydrolyzed in 8h. The relationships among the rigidity or the conformation and the thrombolytic activity in vivo and the stability to enzyme-induced hydrolysis in vitro of the cyclopeptides were discussed.
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彭师奇, Ming Zhao, a Chao Wang, a Jiangyuan Liu, a Kexiang Zhou c and Shiqi Peng b, *
Bioorganic & Medicinal Chemistry 12(2004)2275-2286,-0001,():
-1年11月30日
The in vitro and in vivo thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH, its analogs and the related peptides were assayed. The results indicate that when 5Lys of Ala-Arg-Pro-Ala-Lys-OH is changed into 5Arg, and 3Lys of Pro-Ala-Lys-OH is changed into 3Arg the thrombolytic activities are collapsed; when Pro-Ala-Lys-OH is changed into Ala-Pro-Lys-OH, and Ala-Arg-Pro-Ala-Lys-OH is changed into Ala-Arg-Ala-Pro-Lys-OH the thrombolytic activities are also collapsed; when 5Lys of Ala-Arg- Pro-Ala-Lys-OH is changed into 5nLeu the thrombolytic activities are again collapsed. All of the results indicate that for the thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH and the related peptides Pro-Ala-Lys-OH exhibits either amino acid composition specificity or sequence specificity. The composition and sequence specificity of Pro-Ala-Lys-OH reflects its rule as the pharmacophore of P6A and the related peptides.
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【期刊论文】The synthesis and immunosuppressive activities of steroid-urotoxin linkers
彭师奇, Chao Wang, b Ming Zhao, b Xuecai Qiub and Shiqi Peng a, *
Bioorganic & Medicinal Chemistry 12(2004)4403-4421,-0001,():
-1年11月30日
as prolongation of heterotopic transplanted cardiac tissue survival in vivo, inhibitory effects on phagocytosis of mouse peritoneal macrophages and concanavalin (ConA) or lipopolysaccharide (LPS) induced proliferation of mouse spleen lymphocytes in vitro show that at the comparable concentrations the immunosuppressive activities of the steroid-urotoxin linkers 7a-d, 8a-d, 9a,b, and 10a,b were higher than that of hydrocortisone, prednisolone, and the urotoxins alone, as well as significantly higher than that of the mixture of hydrocortisone and urotoxins or prednisolone and urotoxins. The so-called 'permissive action' may be responsible for the enhancement of the mentioned bioactivities of the steroid–urotoxin linkers 7a-d, 8a-d, 9a,b, and 10a,b.
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【期刊论文】Synthesis and Bioactivities of Nitronyl Nitroxide and RGD Containing Pseudopeptides
彭师奇, Junling Liu, Ming Zhao, Chao Wang and Shiqi Peng*
Bioorganic & Medicinal Chemistry Letters 13(2003)4065-4069,-0001,():
-1年11月30日
1-(1′,3′-Dioxyl-4′,4′,5′,5′-tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetic acid (3), and 1-(1′,3′-dioxyl-4′,4′,5′,5′-tetramethyldihydroimidazol-2′-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized. The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and RGDF the corresponding bioactivities for both of 3 and RGD peptides can be remained completely. The present combinations provided a beneficial strategy for simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of RGD peptides in the conformational researches.
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