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1.
Binding of small basic peptides to membranes containing acidic lipids: theoretical models and experimental results. 总被引:4,自引:4,他引:0
We measured directly the binding of Lys3, Lys5, and Lys7 to vesicles containing acidic phospholipids. When the vesicles contain 33% acidic lipids and the aqueous solution contains 100 mM monovalent salt, the standard Gibbs free energy for the binding of these peptides is 3, 5, and 7 kcal/mol, respectively. The binding energies decrease as the mol% of acidic lipids in the membrane decreases and/or as the salt concentration increases. Several lines of evidence suggest that these hydrophilic peptides do not penetrate the polar headgroup region of the membrane and that the binding is mainly due to electrostatic interactions. To calculate the binding energies from classical electrostatics, we applied the nonlinear Poisson-Boltzmann equation to atomic models of the phospholipid bilayers and the basic peptides in aqueous solution. The electrostatic free energy of interaction, which arises from both a long-range coulombic attraction between the positively charged peptide and the negatively charged lipid bilayer, and a short-range Born or image charge repulsion, is a minimum when approximately 2.5 A (i.e., one layer of water) exists between the van der Waals surfaces of the peptide and the lipid bilayer. The calculated molar association constants, K, agree well with the measured values: K is typically about 10-fold smaller than the experimental value (i.e., a difference of about 1.5 kcal/mol in the free energy of binding). The predicted dependence of K (or the binding free energies) on the ionic strength of the solution, the mol% of acidic lipids in the membrane, and the number of basic residues in the peptide agree very well with the experimental measurements. These calculations are relevant to the membrane binding of a number of important proteins that contain clusters of basic residues. 相似文献
2.
Population genetics and phylogenetics of DNA sequence variation at multiple loci within the Drosophila melanogaster species complex 总被引:14,自引:1,他引:13
Two regions of the genome, a 1-kbp portion of the zeste locus and a 1.1-
kbp portion of the yolk protein 2 locus, were sequenced in six individuals
from each of four species: Drosophila melanogaster, D. simulans, D.
mauritiana, and D. sechellia. The species and strains were the same as
those of a previous study of a 1.9-kbp region of the period locus. No
evidence was found for recent balancing or directional selection or for the
accumulation of selected differences between species. Yolk protein 2 has a
high level of amino acid replacement variation and a low level of
synonymous variation, while zeste has the opposite pattern. This contrast
is consistent with information on gene function and patterns of codon bias.
Polymorphism levels are consistent with a ranking of effective population
sizes, from low to high, in the following order: D. sechellia, D.
melanogaster, D.mauritiana, and D. simulans. The apparent species
relationships are very similar to those suggested by the period locus
study. In particular, D. simulans appears to be a large population that is
still segregating variation that arose before the separation of D.
mauritiana and D. sechellia. It is estimated that the separation of
ancestral D. melanogaster from the other species occurred 2.5-3.4 Mya. The
separations of D. sechellia and D. mauritiana from ancestral D. simulans
appear to have occurred 0.58- 0.86 Mya, with D. mauritiana having diverged
from ancestral D. simulans 0.1 Myr more recently than D. sechellia.
相似文献
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Using polyethylene glycol and dextran as osmotic stressing agents, the concentrations of hyaluronate and heparin were measured as a function of osmotic pressure II over the range of 0.03 to nearly 50 atmospheres. The experimental results were analyzed in terms of the Donnan osmotic pressure, the virial expansion, and Flory's first neighbor interaction parameter. In addition, II was looked at as a function of the reciprocal cube root of the concentration, which represents an average intermonomer spacing at high concentrations. The decay lengths in the so-called hydration region were found to be around 2.6 A and negligibly salt dependent. In the electrostatically dominated region the decay lengths were found to be dependent on the ionic strength, but not simply so. The osmotic compressibilities were also calculated, and were compared to compressibility data of corneal stroma and articular cartilage. These latter compressibilities were close to those for the pure hyaluronate and heparin, strengthening the evidence that glycosaminoglycans (GAGs) are largely responsible for connective tissue compressibility. Higher compressibilities for previously reported GAG data is thought to be related to the protein content of those samples. 相似文献
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C García-Vielma MI Dávila-Rodríguez F Hernández-Garza RM Cerda-Flores 《Biotechnic & histochemistry》2016,91(2):102-107
We performed a hospital-based, unmatched case-control study to investigate the association between progressive stages of cervical neoplasia and digital analysis of cell proliferation by silver stained nucleolus organizer region associated proteins (AgNORs). We measured cell proliferation levels in the cervical epithelial cells of 10 women with low grade squamous intraepithelial lesions (LG-SIL), eight with high grade squamous intraepithelial lesions (HG-SIL), 11 with cervical cancer (CC) and eight with no cervical lesions (controls) using the AgNORs technique. Cell proliferation was measured by digital image analysis (DIA). DIA revealed increased total areas of AgNORs in HG-SIL and CC compared to LG-SIL and control patients. AgNORs with a kidney or cluster shape exhibited greater areas than those with a spherical or long shape. We propose a cut-off of 118 pixels to differentiate benign (control and LG-SIL) from malignant (HG-SIL and CC) lesions. DIA of AgNORs is a simple and inexpensive method for studying proliferation. The increased total area of AgNORs in malignant lesions provides information regarding cell behavior and may be related to cervical carcinogenesis; however, further validation studies are required to establish its usefulness in cytological analysis. 相似文献
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1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D- galactofuranosidase inhibitors
Marino C; Marino K; Miletti L; Manso Alves MJ; Colli W; de Lederkremer RM 《Glycobiology》1998,8(9):901-904
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design
of inhibitors, since beta-D-galactofuranose is a constituent of important
parasite glycoconjugates but is not present in the host mammals. With this
aim, we have synthesized for the first time alkyl, benzyl and aryl
1-thio-beta-D-galactofuranosides by condensation of
penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols,
in the presence of SnCl4as catalyst. The complete chemical and
spectroscopical characterization of these compounds showed that the
reaction was stereoselective. Debenzoylation with sodium methoxide afforded
the beta-S-galactofuranosides in high yield. The thioglycosides were tested
as inhibitors of the beta-D- galactofuranosidase of Penicillium fellutanum,
using for the first time 4-nitrophenyl-beta-D-galactofuranoside as
chromogenic substrate. The 4- aminophenyl-1-thio-beta-D-galactofuranoside,
obtained by catalytic hydrogenation of the nitrophenyl derivative, was the
best inhibitor being then an adequate ligand for the preparation of an
affinity phase aimed at the isolation of beta-d-galactofuranosidases from
different sources. Also the inhibitory activity of d-galactono-1, 4-lactone
was shown.
相似文献
10.
Rebecca Vicente-Steijn Roderick W. C. Scherptong Boudewijn P. T. Kruithof Sjoerd N. Duim Marie Jose T. H. Goumans Lambertus J. Wisse Bin Zhou William T. Pu Robert E. Poelmann Martin J. Schalij Michelle D. Tallquist Adriana C. Gittenberger-de Groot Monique RM Jongbloed 《PloS one》2015,10(9)