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51.
52.
John D. Wade Marc N. Mathieu Mary Macris Geoffrey W. Tregear 《International journal of peptide research and therapeutics》2000,7(2):107-112
Summary Base-induced aspartimide (cyclic imide) and subsequent base adduct formation in the Fmoc-solid phase synthesis of sensitive
sequences are serious side reactions that are difficult to both anticipate and control. The effect of extended treatment of
piperazine as Nα-Fmoc deprotection reagent on two sensitive peptide sequences was examined. For comparison, other bases were also investigated,
including piperidine, 1-hydroxypiperidine, tetrabutylammonium fluoride, and 1,8-diazabicyclo[5.4.0]undec-7-ene. The results
showed that all bases induced varying degrees of both aspartimide and, in some cases, base adduct formation, although piperazine
caused the least side reaction. Use ofN-(2-hydroxy-4-methoxybenzyl) peptide backbone amide protection was confirmed to confer complete protection against side reaction.
In the absence of such protection, for all bases, the use of 1-hydroxybenzotriazole as additive had some, but not complete,
beneficial effect in further reducing side reaction. Best results were obtained with piperazine containing 0.1M 1-hydroxybenzotriazole
indicating that this reagent merits serious consideration for Nα-deprotection in the Fmoc-solid phase synthesis of base-sensitive sequences. A further advantage of this reagent is that it
causes little racemisation of resin-bound C-terminal cysteine, an occasionally serious base-mediated problem in Fmoc-solid
phase assembly.
A preliminary account of this work was presented at the 25th European Peptide Symposium, Budapest, Hungary, 1998. 相似文献
53.
Experiments have been undertaken to correlate physiological changes, observed in two YC8 cells variants (P and L) and some of their immunological and enzymatic properties. These cell lines show different responses towards antilymphocyte and anti-Moloney sera. Subcellular fractionations have been made. The A fractions (d: 1.14/1.16) have the highest ouabain-inhibited Mg2+-stimulated (Na+-K+)-dependent ATPase and galactosyltransferase activities. Some properties of the latter enzyme have been studied: whereas optima pH and requirements for Mn2+ ions have been found to be the same for both cell line enzymes, on the contrary, different kinetic parameters have been shown with respect to sugar donor (UDP-galactose) on endogeneous or exogeneous (ovomucoid) acceptors. Apparent Km for UDP-galactose is 1.7 × 10−6 M (P-cells) and 3.3 × 10−6 M (L-cells), on endogeneous acceptors, and P-cell V max < L-cell V max; on ovomucoid it is 0.61 × 10−6 M, for both cell lines. These results suggest the presence on L-cells of more endogeneous acceptor sites, the higher affinity of P-cells for UDP-galactose being balanced by less endogeneous acceptor sites for galactose. When ovomucoid is added, galactose transfer on endogeneous acceptor sites of both cells is negligible. Apparent Km for ovomucoid is 8.6 × 10−5 M (P-cells) and 4.3 × 10−5 M (L-cells). These data support the above-mentioned hypothesis: L-cell enzymes would be more rapidly saturated than P-cell enzymes because of the higher number of endogeneous sites on L-cells.This supposed acquired character of L-cells as well as their immunological behaviour could explain the modified properties of L-cells as compared to P-cells. 相似文献
54.
55.
A simplistic, yet often used, view of protein stability is that amino acids attract other amino acids with similar polarity, whereas nonpolar and polar side chains repel. Here we show that nonpolar/polar interactions, namely Val or Ile bonding to Lys or Arg in alpha-helices, can in fact be stabilizing. Residues spaced i, i + 4 in alpha-helices are on the same face of the helix, with potential to favorably interact and stabilize the structure. We observe that the nonpolar/polar pairs Ile-Lys, Ile-Arg, and Val-Lys occur in protein helices more often than expected when spaced i, i + 4. Partially helical peptides containing pairs of nonpolar/polar residues were synthesized. Controls with i, i + 5 spacing have the residues on opposite faces of the helix and are less helical than the test peptides with the i, i + 4 interactions. Experimental circular dichroism results were analyzed with helix-coil theory to calculate the free energy for the interactions. All three stabilize the helix with DeltaG between -0.14 and -0.32 kcal x mol(-1). The interactions are hydrophobic with contacts between Val or Ile and the alkyl groups in Arg or Lys. Side chains such as Lys and Arg can thus interact favorably with both polar and nonpolar residues. 相似文献
56.
The suggestion that the electron acceptor A1 in plant photosystem I (PSI) is a quinone molecule is tested by comparisons with the bacterial photosystem. The electron spin polarized (ESP) EPR signal due to the oxidized donor and reduced quinone acceptor (P
870
+
Q-) in iron-depleted bacterial reaction centers has similar spectral characteristics as the ESP EPR signal in PSI which is believed to be due to P
700
+
A
1
-
, the oxidized PSI donor and reduced A1. This is also true for better resolved spectra obtained at K-band (24 GHz). These same spectral characteristics can be simulated using a powder spectrum based on the known g-anisotropy of reduced quinones and with the same parameter set for Q- and A1
-. The best resolution of the ESP EPR signal has been obtained for deuterated PSI particles at K-band. Simulation of the A1
- contribution based on g-anisotropy yields the same parameters as for bacterial Q- (except for an overall shift in the anisotropic g-factors, which have previously been determined for Q-). These results provide evidence that A1 is a quinone molecule. The electron spin polarized signal of P700
+ is part of the better resolved spectrum from the deuterated PSI particles. The nature of the P700
+ ESP is not clear; however, it appears that it does not exhibit the polarization pattern required by mechanisms which have been used so far to explain the ESP in PSI.Abbreviations hf
hyperfine
- A0
A0 acceptor of photosystem I
- A1
A1 acceptor of photosystem I
- Brij-58
polyoxyethylene 20 cetyl ether
- CP1
photosystem I particles which lack ferridoxin acceptors
- ESP
electron spin polarized
- EPR
electron paramagnetic resonance
- I
intermediary electron acceptor, bacteriopheophytin
- LDAO
lauryldimethylamine
- N-oxide, P700
primary electron donor of photosystem I
- PSI
photosystem I
- P700
T
triplet state of primary donor of photosystem I
- P870
primary donor in R. sphaeroides reaction center
- Q
quinore-acceptor in photosynthetic bacteria
- RC
reaction center 相似文献
57.
Marjan Shafaati Natalia Mast Olof Beck Rima Nayef Gun Young Heo Linda Bj?rkhem-Bergman Dieter Lütjohann Ingemar Bj?rkhem Irina A. Pikuleva 《Journal of lipid research》2010,51(2):318-323
Cholesterol 24S-hydroxylase (CYP46A1) is of key importance for cholesterol homeostasis in the brain. This enzyme seems to be resistant toward most regulatory factors and at present no drug effects on its activity have been described. The crystal structures of the substrate-free and substrate-bound CYP46A1 were recently determined (Mast et al., Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc. Natl. Acad. Sci. USA. 2008. 105: 9546–9551). These structural studies suggested that ligands other than sterols can bind to CYP46A1. We show here that the antifungal drug voriconazole binds to the enzyme in vitro and inhibits CYP46A1-mediated cholesterol 24-hydroxylation with a Ki of 11 nM. Mice treated with daily intraperitoneal injections of voriconazole for 5 days had high levels of voriconazole in the brain and significantly reduced brain levels of 24S-hydroxycholesterol. The levels of squalene, lathosterol, and HMG-CoA reductase mRNA were reduced in the brain of the voriconazole-treated animals as well, indicating a reduced cholesterol synthesis. Most of this effect may be due to a reduced utilization of cholesterol by CYP46A1. One of the side-effects of voriconazole is visual disturbances. Because CYP46A1 is also expressed in the neural retina, we discuss the possibility that the inhibition of CYP46A1 by voriconazole contributes to these visual disturbances. 相似文献
58.
Oxygen consumption in Mn-depleted photosystem II (PSII) preparations under continuous and pulsed illumination is investigated. It is shown that removal of manganese from the water-oxidizing complex (WOC) by high pH treatment leads to a 6-fold increase in the rate of O2 photoconsumption. The use of exogenous electron acceptors and donors to PSII shows that in Mn-depleted PSII preparations along with the well-known effect of O2 photoreduction on the acceptor side of PSII, there is light-induced O2 consumption on the donor side of PSII (nearly 30% and 70%, respectively). It is suggested that the light-induced O2 uptake on the donor side of PSII is related to interaction of O2 with radicals produced by photooxidation of organic molecules. The study of flash-induced O2 uptake finds that removal of Mn from the WOC leads to O2 photoconsumption with maximum in the first flash, and its yield is comparable with the yield of O2 evolution on the third flash measured in the PSII samples before Mn removal. The flash-induced O2 uptake is drastically (by a factor of 1.8) activated by catalytic concentration (5-10 μM, corresponding to 2-4 Mn per RC) of Mn2+, while at higher concentrations (> 100 μM) Mn2+ inhibits the O2 photoconsumption (like other electron donors: ferrocyanide and diphenylcarbazide). Inhibitory pre-illumination of the Mn-depleted PSII preparations (resulting in the loss of electron donation from Mn2+) leads to both suppression of flash-induced O2 uptake and disappearance of the Mn-induced activation of the O2 photoconsumption. We assume that the light-induced O2 uptake in Mn-depleted PSII preparations may reflect not only the negative processes leading to photoinhibition but also possible participation of O2 or its reactive forms in the formation of the inorganic core of the WOC. 相似文献
59.
Photoinhibition of photosynthesis was studied in young and mature detached sun needles of cypress under high irradiance (HI) of about 1 900 mol m–2 s–1. The degree of photoinhibition was determined by means of the ratio of variable to maximum chlorophyll (Chl) fluorescence (Fv/Fm) and electron transport measurements. Compared with the mature needles, the young needles, containing about half the amount of Chl a+b per unit area, exhibited a higher proportion of total carotenoids (Car) as xanthophyll cycle pigments and had an increased ratio of Car/Chl a+b. The potential efficiency of photosystem (PS) 2, Fv/Fm, markedly declined in HI-treated young needles without significant increase of F0 level. In contrast, the Fv/Fm ratio declined with significant increase of F0 level in mature needles. In isolated thylakoids, the rate of whole chain and PS2 activity markedly decreased in young HI-needles in comparison with mature needles. A smaller inhibition of PS1 activity was observed in both needles. In the subsequent dark incubation, fast recovery was found in both needle Types that reached maximum PS2 efficiencies similar to those observed in non-photoinhibited needles. The artificial exogenous electron donors DPC, NH2OH, and Mn2+ failed to restore the HI-induced loss of PS2 activity in mature needles, while DPC and NH2OH significantly restored it in young needles. Hence, HI-inactivation was on the donor side of PS2 in young needles and on the acceptor side of PS2 in mature needles. Quantification of the PS2 reaction centre proteins D1 and 33 kDa protein of water splitting complex following HI-exposure of needles showed pronounced differences between young and mature needles. The large loss of PS2 activity in HI-needles was due to the marked loss of D1 protein of the PS2 reaction centre in mature needles and of the 33 kDa protein in young needles. 相似文献
60.
M. Bertamini L. Zulini R. Zorer K. Muthuchelian N. Nedunchezhian 《Photosynthetica》2007,45(3):426-432
Photoinhibition under irradiance of 2 000 μmol m−2 s−1 (HI) was studied in detached control (C) and water deficit (WD) leaves of grapevine (Vitis vinifera L.) plants. The degree of photoinhibition was determined by means of the ratio of variable to maximum chlorophyll (Chl) fluorescence
(Fv/Fm) and electron transport measurements. The potential efficiency of photosystem (PS) 2, Fv/Fm, marginally declined under HI in WD-leaves without significant increase of F0. In contrast, Fv/Fm ratio declined markedly with significant increase of F0 in C-leaves. In isolated thylakoids, the rate of whole chain and PS2 activity under HI were more decreased in C-than WD-leaves.
The artificial exogenous electron donors diphenyl carbazide, NH2OH, and Mn2+ failed to restore the HI-induced loss of PS2 activity in both C-and WD-leaves. Thus HI operates at the acceptor side of PS2
in both leaf types. Quantification of the PS2 reaction centre protein D1 following HI exposure of leaves showed pronounced
differences between C-and WD-leaves. The marked loss of PS2 activity under HI of C-leaves was due to the marked loss of D1
protein of the PS2 reaction centre. 相似文献