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31.
J Markussen I Diers A Engesgaard M T Hansen P Hougaard L Langkjaer K Norris U Ribel A R S?rensen E S?rensen 《Protein engineering》1987,1(3):215-223
It has previously been found that insulins, to which positive charge has been added by substitutions in position B30, thus raising the isoelectric point towards pH 7, had a prolonged action when injected as slightly acidic solutions because such derivatives crystallize very readily upon neutralization. Positive charge has now been added by substituting the B13 and A17 glutamic acid residues with glutamines and B27 threonine with lysine or arginine. These substitutions were introduced by site-specific mutagenesis in a gene coding for a single-chain insulin precursor. By tryptic transpeptidation the single-chain precursors were transformed to the double-chain insulin structure, concomitantly with incorporation of residue B30. Thus insulins combining B13 glutamine, A17 glutamine and B27 lysine or arginine with B30 threonine, threonine amide or lysine amide were synthesized. The time course of blood glucose lowering effect and the absorption were studied after subcutaneous injection in rabbits and pigs. The prolonged action of B30-substituted insulins was markedly enhanced by B27 lysine or arginine substitutions and by B13 glutamine. The B27 residue is located on the surface of the hexamer, so a basic residue in this position presumably promotes the packing of hexamers at neutral pH. The B13 residues cluster in the centre of the hexamer. When the electrostatic repulsive forces from six glutamic acid residues are abolished by substitution with glutamine, a stabilization of the hexamer can be envisaged.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
32.
I P Grigor'ev A A Neokesari?ski? 《Biulleten' eksperimental'no? biologii i meditsiny》1986,102(9):288-289
The effects of different concentrations of L-ascorbic acid (Asc) on Na+-dependent binding of 3H-GABA and 3H-DL-glutamic acid to rat brain cortical synaptosomes were studied. Asc, at a concentration nearly equal to brain extracellular one (3 X 10(-4) M), had no effect on specific and nonspecific 5H-GABA binding. At higher concentrations (10(-3) M) Asc strongly inhibited, and at lower concentrations (10(-6) M) considerably stimulated 3H-GABA binding. At a concentration of 10(-5)-10(-3) M Asc tended to decrease 3H-DL-glutamic acid binding. 相似文献
33.
D G Astaf'ev I V Maianskaia A K Akatov A N Maianski? 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1986,(7):48-51
In investigations based on the use of a highly sensitive test system permitting the detection of normal human antibodies to S. aureus peptidoglycan, the antigenic relationships between the peptidoglycans of S. aureus and other representatives of the genus Staphylococcus have been studied. Among other staphylococcal species, S. simulans, S. xylosus, S. hyicus, S. cohnii, S. hyicus s. s. chromogenes have been found to possess peptidoglycans most closely related to S. aureus peptidoglycans, while S. warneri and S. epidermidis peptidoglycans have proved to be least closely related to it. 相似文献
34.
ESR spectra of gamma-irradiated and frozen at 77 K human oxyhemoglobin and partially denaturated methemoglobin solutions were analysed. The quartet signal ascribed to the anion-radical of proximal histidine was shown to dominate in the spectra of both solutions. The spectra of methemoglobin solution irradiated with relatively small doses have an intensive singlet ascribed to the stabilized electron. The formation mechanism of free radicals is discussed. 相似文献
35.
Interaction between cytotoxin of the Central Asia cobra venom and dimiristoylphosphatidylcholine bilayer depending on its phase state was studied by ESR with spin label. A conclusion can be drawn that the efficiency of cytotoxin effect on the membranes depends on their phase state. Cytotoxin molecules are incorporated into myophile region of the bilayer, only if the latter is in the liquid crystal state. The interaction between cytotoxins and lipids of the bilayer in a gel state is in the main conditioned by electrostatic forces. 相似文献
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Indomethacin and substance BW-755C in experiments on isolated myometrium striae of pregnant white rats exert an inhibiting effect on the contractile uterus function due to inhibition of cyclooxygenase or lipoxygenase ways of the arachidonic acid transformation. Prostaglandin F2 alpha is sensitive to functioning of the cyclooxygenase and lipoxygenase ways of the arachidonic acid transformation, while oxytocin--only lipoxygenase one. Conclusions rest on results from multiparametric analysis of the contractile uterus function suggested by authors and confirmed by the pattern recognition method--the Karunen-Loev orthogonal decomposition. 相似文献
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