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21.
Sokolov AV Ageeva KV Kostevich VA Berlov MN Runova OL Zakharova ET Vasilyev VB 《Biochemistry. Biokhimii?a》2010,75(11):1361-1367
This paper describes formation of complexes of ceruloplasmin (CP) with such proteins of the serprocidin family as azurocidin
(CAP37), neutrophilic elastase (NE), cathepsin G (CG), and proteinase 3 (PR3). We present evidence that serprocidins form
complexes with CP at a molar ratio 1: 1. Phenylmethylsulfonyl fluoride, a serine protease inhibitor, did not prevent the interaction
of serprocidins with CP in the course of SDS-free disc electrophoresis. CP affected the activities of NE, CG, and PR3 as a
competitive inhibitor with K
i ≈ 1 μM. Inhibitory effect of CP depended on ionic strength of the solution and was negligible at NaCl concentrations above
300 mM. In the mode of competitive inhibitors serprocidins suppressed oxidase activity of CP towards p-phenylenediamine. CAP37
displayed the strongest inhibitory effect (K
i ≈20 nM). Upon adding various serprocidins to human, rat, rabbit, dolphin, dog, horse, and mouse plasma only CAP37 would form
a complex with CP. Synthetic peptide RKARPRQFPRRR (5–13, 61–63 CAP37) displaced CAP37 from its complex with CP. Adding CAP37
to the triple complex formed by CP, lactoferrin, and myeloperoxidase resulted in displacement of the latter from the complex.
The dissociation constant of CAP37 with immobilized CP was 13 nM. Therefore, among serprocidins CAP37 can be regarded as the
specific partner of CP. 相似文献
22.
V. I. Vasilyev 《Moscow University Biological Sciences Bulletin》2007,62(1):44-48
In autumn, from March until May 1988 in the Patagonian shelf and slope zones, the system of the water current was modified and water temperature decreased. The biomass of seston and abundance of zooplankton decreased simultaneously, especially those of the subantactric species Calanus simillimus. Zooplankton organisms started their descent to deeper waters. The Antarctic species Rhincalanus gigas was common in the upper layers in March. In May, R. gigas was rare and occurred in deeper layers. Subtropical zooplankton species dominated in the shelf zone, while subantartic species dominated in the slope zone within the Falkland current. In May, the abundance of shelf species in the slope zone increased due to weakening of the Falkland current and its dislocation to the east. The zooplankton biomass and abundance increased at the zone of water divergence in the east and at the slope frontal zone in the west. 相似文献
23.
Biftu T Feng D Qian X Liang GB Kieczykowski G Eiermann G He H Leiting B Lyons K Petrov A Sinha-Roy R Zhang B Scapin G Patel S Gao YD Singh S Wu J Zhang X Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(1):49-52
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. 相似文献
24.
Kowalchick JE Leiting B Pryor KD Marsilio F Wu JK He H Lyons KA Eiermann GJ Petrov A Scapin G Patel RA Thornberry NA Weber AE Kim D 《Bioorganic & medicinal chemistry letters》2007,17(21):5934-5939
Various beta-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall pharmacokinetic profiles in preclinical species. Moreover, in vivo efficacy in an oral glucose tolerance test in lean mice is demonstrated. 相似文献
25.
Biftu T Scapin G Singh S Feng D Becker JW Eiermann G He H Lyons K Patel S Petrov A Sinha-Roy R Zhang B Wu J Zhang X Doss GA Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(12):3384-3387
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile. 相似文献
26.
O. S. Tikhomirova N. A. Grudinina V. I. Golubkov M. Yu. Mandelshtam V. B. Vasilyev 《Russian Journal of Genetics》2007,43(9):1053-1057
Screening of patients with familial breast cancer from St. Petersburg for BRCA1 gene mutations resulted in identification of three mutations (4146del3, 2761delA, and A622V) and two polymorphisms (P871L and S1436S). Mutations 4146del3 and 2761delA are novel, never previously described elsewhere. Deletion 2761delA produces a reading frame shift, premature protein synthesis termination and can cause predisposition for breast cancer. Deletion 4146del3 does not cause a frame shift, but can result not only in the disappearance of amino acid residue (D1343del) in the BRCA1 protein but also in alteration of folding of the protein, entailing loss of its functional activity. Two variants of nucleotide sequence observed in the number of patients were classified as DNA polymorphisms (P871L and S1436S) rather than mutations as they were not tightly associated with the increased risk of breast cancer. 相似文献
27.
28.
Elena?G.?RudikovskayaEmail author Lyubov?V.?Dudareva Aleksandr?A.?Shishparenok Aleksandr?V.?Rudikovskii 《Acta Physiologiae Plantarum》2015,37(11):238
For the first time, we have studied the polyphenolic profile of fruits of Siberian crabapple and its hybrids (F1, F2, and F3) with domestic apple cultivated in East Siberia. It is shown that the chemical composition of polyphenolics of Siberian crabapple fruits is overwhelmingly characteristic of the genus Malus; on the other hand, it has clearly identifiable features: low content of flavan-3-ols and derivatives of cinnamic acid; high content of procyanidin B1, phloridzin, anthocyanes, and quercetin glycosides. Procyanidin B2 was not found in both peel and flesh of Siberian crabapple. In the case of hybridization with domestic apple, the fruits of resulting cultivars show a substantial change in the flavan-3-ol content ratio because of the synthesizing of procyanidin B2 in tissues and an increase in (?)-epicatechin content. 相似文献
29.
30.
Noy A 《Current opinion in chemical biology》2011,15(5):710-718
Single molecule force spectroscopy presents a deceptively simple approach to probing interaction between molecules and molecular assemblies on the nanoscale by measuring forces that it takes to pull the molecules apart. Yet, a more detailed analysis reveals a wealth of different behaviors and interesting physics. This article aims to explore basic physical concepts behind these experiments from a strictly practical point of using these data to extract meaningful information about the interactions. It also focuses on different loading regimes in these experiments, different kinetics that they cause, and different data interpretation that is required for measurements in those regimes. 相似文献