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1.
Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-n-Cys(Trt)-OBut] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK1= 2.35–2.84) and to terminal amino group (pK2= 5.61–6.93); pK1, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK2, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH+3-) formation. 相似文献
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Kvacheva ZB Shukanova NA Votyakov VI Lobanok ES Vorobei AV Nikolaeva SN 《Bulletin of experimental biology and medicine》2003,135(4):384-387
Membranotropic amphiphilic chromophore merocyanine 540 sensitized photodynamic inhibition of drug-resistant and sensitive variants of type I herpes simplex virus in cultured Vero cell. Optimal conditions of photodamage to virus particles and infected cells were determined (merocyanine 540 concentration 1 M, illumination dose 32.5-65.0 kJ/m2, exposure at early stages of infection). Infected cells actively bind the photosensitizer, which explains their selective photodamage. 相似文献
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A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia 下载免费PDF全文
Zhengyuan Wang Lena Diaw Lita Freeman Krupa Desai Michael Dizon Darlene Allen Colin Cunnington Keith M. Channon Jacqueline Milton Stephen W. Hartley Vikki Nolan Gregory J. Kato Martin H. Steinberg David Goldman James G. Taylor VI 《American journal of hematology》2014,89(2):187-193
GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
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V. I. Votyakov I. R. Erokhina T. V. Amvros'eva 《Bulletin of experimental biology and medicine》1989,107(5):687-691
Department of Inhibitors of Viral Activity, Belorussian Research Institute of Epidemiology and Microbiology, Ministry of Health of the Belorussian SSR, Minsk. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 5, pp. 595–598, May, 1989. 相似文献
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Harmatz P Ketteridge D Giugliani R Guffon N Teles EL Miranda MC Yu ZF Swiedler SJ Hopwood JJ;MPS VI Study Group 《Pediatrics》2005,115(6):e681-e689
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Harmatz P Kramer WG Hopwood JJ Simon J Butensky E Swiedler SJ;Mucopolysaccharidosis VI Study Group 《Acta paediatrica (Oslo, Norway : 1992). Supplement》2005,94(447):61-8; discussion 57
AIM: Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme-N-acetylgalactosamine 4-sulphatase (ASB). Enzyme replacement therapy with recombinant human ASB (rhASB) has been studied in a randomized, double-blind, two-dose (0.2 and 1.0 mg/kg/week) phase I/II study (n = 7) followed by an open-label single dose (1.0 mg/kg/week) extension study. We report the pharmacokinetic profile of rhASB and the impact of antibody development. METHODS: Pharmacokinetic analysis was performed at weeks 1, 2, 12, 24, 83, 84 and 96. Infusions were administered over 4 hours using a ramp-up protocol. Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan (GAG) concentrations were determined. RESULTS: The area under the plasma concentration-time curve (AUC(0-t)) for the high-dose group increased from week 1 to week 2, but remained unchanged at weeks 12 and 24. A large difference in mean AUC(0-t) was observed between the low- and high-dose groups. Pharmacokinetic results at weeks 83, 84 and 96 were similar to those at week 24. Six patients developed antibodies to rhASB. One patient developed high antibody levels in combination with a high ASB concentration, while a second patient also developed high antibody levels with undetectable ASB concentrations. Antibodies from the second patient blocked detection of ASB. By week 72, antibody levels had decreased in all patients. The high-dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose (70% versus 55% at 24 weeks). Antibody levels did not appear to influence urinary GAG concentrations. CONCLUSION: Pharmacokinetic parameters appear to be independent of the duration of treatment and are not linear between the 0.2 and 1.0 mg/kg/week doses. Antibodies to rhASB develop in most patients, but their concentration decreases over time. Antibody formation may influence pharmacokinetic parameters during the early phases of treatment, although it appears to have limited impact on biochemical efficacy. 相似文献