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1.
M Chorev E Roubini M E Goldman R L McKee S W Gibbons J E Reagan M P Caulfield M Rosenblatt 《International journal of peptide and protein research》1990,36(5):465-470
Position 18 in a parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2 (ii), was shown to tolerate substitutions by a range of amino acids with retention of inhibitory activity. The effects of hydrophobic substitutions at this position as a means of enhancing binding interactions with the receptor were evaluated. Substitution of Nle at position 18 with either D-Ala, D-Trp, or L-Trp in analog ii or with Trp (D or L) in the recently reported, highly potent antagonist, [Nle8,18,D-Trp12,Tyr34]bPTH(7-34)NH2 (in vitro activities; Kb = 15 nM and Ki = 125 nM), was performed. In terms of activity on renal receptors, one antagonist, [Nle8,D-Trp12,18,Tyr34]bPTH(7-34)NH2, is the most active in vitro PTH antagonist yet reported (Kb = 4 nM; Ki = 30 nM). The rationale for design of this antagonist and the conclusions regarding PTH-receptor interactions are discussed. 相似文献
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Auxotrophic mutants of Candida albicans FC18 were induced by a combination of treatments with nitrous acid and UV irradiation. Arginine (Arg-), histidine (His-) and methionine/cysteine (MetA-) auxotrophs were recovered by this means. The Arg- auxotrophs lacked active argininosuccinate lyase (EC 4.3.2.1), the enzyme catalysing the final step in arginine biosynthesis. Thus the locus may be designated arg-4. The mutant strains bearing this mutation did not form germ tubes unless the germination medium contained arginine. 相似文献
4.
The stability of different regions of the beta heavy chain of dynein has been investigated by examining the perturbing effects of methanol, temperature, salt, and nucleotide on the pattern of tryptic digestion. In standard low-salt medium, tryptic proteolysis cleaves the beta heavy chain into three principal polypeptides of 130, 215, and 110 kDa, with the 215-kDa central peptide containing the ATP binding site as well as the vanadate and iron photocleavage sites (Mocz, G., Tang, W.-J. Y., & Gibbons, I. R. (1988) J. Cell Biol. 106, 1607-1614). The 130-kDa peptide is the most stable, and its susceptibility to trypsin appears unaffected by methanol concentrations up to 25% or temperatures up to 45 degrees C, although a 5-kDa region at one end is lost in the presence of salt (greater than 20 mM NaCl). The 215-kDa tryptic peptide contains two regions of different stability: its 123-kDa portion adjoining the 130-kDa peptide is destabilized by mild heat (37 degrees C) or by 25% methanol and becomes digested away to leave the more stable region of 92 kDa that is located toward the 110-kDa peptide and retains the V1 photocleavage site and most of the ATP binding site. The 110-kDa peptide is the least stable and at 37 degrees C, or in the presence of low concentrations of methanol or salt, it rapidly digested to small peptides. The presence of ATP during digestion of the beta heavy chain retards the formation of the 130- and 215-kDa peptides and also protects the 215-kDa peptide from further digestion at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
N Niccolai M P Miles W A Gibbons 《Biochemical and biophysical research communications》1979,91(1):157-163
We report mono and bi-selective excitation proton relaxation studies of internal motion of three side chaing in a peptide fragment of angiotensin of sequence Tyr1. Ile2. His3. Pro4. Phe5. The motion of this peptide does not satisfy the extreme narrowing conditions and the general approach to the interpretation of proton relaxation rates given here can be used in larger peptides and proteins. 相似文献
6.
A family group of tenS. fuscicollis, housed in a greenhouse and subjected to natural variations in day length, was observed for a period of three months. All
animals ordinarily slept together in the same hutch box. The order in which the various animals emerged in the morning was
almost the precise inverse of the order in which they retired at night. Each of these orders was quite reliable and was related
in nonlinear fashion to age—the ranks of the youngest offspring being the closest to those of the parents. Time of emergence
and eating in the morning consistently preceded sunrise by about 30 min and was initiated by the oldest offspring; retiring
was much more variable and was led by the parents. 相似文献
7.
Rabbit kidney function was assessed in vitro after cryoprotection with either 3 or 4 M dimethyl sulfoxide. The introduction and removal of the cryoprotectant was carried out in a stepwise progressive manner and the removal in a stepwise progressive manner with hypertonic mannitol solutions. This in vitro model can be shown to respond to various ischemic-like states resulting in poor or absent function. Active tubular transport can be demonstrated. It has been used by many authors as an intermediate step prior to the ultimate test of reimplant and contralateral nephrectomy. Variations in the rate of cooling at cryoprotection levels of 3 and 4 M dimethyl sulfoxide concentration (Me2SO) were carried out. In general, at 3 M concentration of Me2SO, creatinine clearance, sodium and glucose reabsorption are preserved with a fair degree of success after cooling to -10, -15, and -20 degrees C in our model, when the rate of cooling to these levels is 1.0 degree C/min. When a cooling rate of 0.5 degree C/min is used, renal function is significantly reduced whether the final temperature is -10, -15, or -20 degrees C. Control rabbit kidneys will tolerate 4 M concentration of Me2SO and give fairly good function. When cooled to -15 or -20 degrees C, there is poor function at 0.1 and 0.5 degrees C/min. Fair function is obtained at the rate of 1 degree C/min to -10 degrees C. Therefore, at cryoprotectant levels of 3 and 4 M Me2SO, kidney function as assayed by in vitro perfusion, is better when the cooling rate is 1.0 degree C/min. 相似文献
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9.
Conformational and thermodynamic aspects of cation binding by the carboxylic ionophore narasin A were studied by circular dichroism (CD). In single-phase solvents, dramatic increases in the maximum differential absorption (delta epsilon) of the C-11 carbonyl were observed upon the binding of K+, Na+ and protons to the free anionic form. These changes were associated with major shifts in the conformation equilibrium between extended and pseudocyclic conformers of narasin. Similar CD changes observed upon the binding of K+ to narasin A in dimyristoylphosphatidylcholine vesicles provided evidence that in the membrane environment, comparable conformation changes were associated with ion binding. Variation of the polar and protic properties of single-phase solvents was also found to influence the delta epsilon of the cation bound species of narasin A, supporting previous evidence for polarity-mediated modulation of conformation. Comparison of cation binding affinities indicated that in both single-phase solvents and liposomes, narasin had a marked equilibrium selectivity for K+ over Na+. 相似文献
10.
The K88 antigen of Escherichia coli specifically adheres to the piglet intestinal cell; a solution of this antigen agglutinates guinea-pig red cells at 4 degrees C. The latter reaction was used as a model of the former, using inhibition of haemagglutination as an index of specific combination with the K88 adhesin. Inhibition was found with mucous glycoproteins and chemical modification of their heterosaccharide residues by mild acid hydrolysis, periodate oxidation or the Smith degradation procedure suggested that the terminal beta-D-galactosyl structure in a heterosaccharide sidechain of a glycoprotein might combine specifically with the K88 adhesin and inhibit haemagglutination. One serum glycoprotein (fetuin), after exposure of its subterminal beta-D-galactosyl residue, also inhibited haemagglutination, but high inhibitory activity was exhibited by some submaxillary glycoproteins in which this structure was absent or not prominent. It was concluded that in some cases inhibition of haemagglutination by glycoprotein was non-specific. No inhibition was found using glycosaminoglycans, glycogen or any simple sugar or glycoside. Sow colostrum was inhibitory but this was associated mainly with its gamma-globulin fraction. Some inhibitory activity was traced to a colostral glycopeptide fraction of low molecular weight but the smaller colostral oligosaccharides were not inhibitory; the composition of these components in sow colostrum is reported. 相似文献