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11.
12.
Alicia P. Higueruelo Adrian Schreyer G. Richard J Bickerton Tom L. Blundell Will R. Pitt 《PloS one》2012,7(12)
Efforts to increase affinity in the design of new therapeutic molecules have tended to lead to greater lipophilicity, a factor that is generally agreed to be contributing to the low success rate of new drug candidates. Our aim is to provide a structural perspective to the study of lipophilic efficiency and to compare molecular interactions created over evolutionary time with those designed by humans. We show that natural complexes typically engage in more polar contacts than synthetic molecules bound to proteins. The synthetic molecules also have a higher proportion of unmatched heteroatoms at the interface than the natural sets. These observations suggest that there are lessons to be learnt from Nature, which could help us to improve the characteristics of man-made molecules. In particular, it is possible to increase the density of polar contacts without increasing lipophilicity and this is best achieved early in discovery while molecules remain relatively small. 相似文献
13.
Douglas G. Gilmour Walter M. Collins Tom L. Fredericksen Willard E. Urban Jr. Paul F. Ward Nancy L. DiFronzo 《Immunogenetics》1986,23(1):1-6
Chickens of Regional Poultry Research Laboratory (RPRL) inbred line 63 regress sarcomas induced by Bryan high-titer Rous sarcoma virus to a greater extent than chickens of line RPRL 100, although these lines are identical for the major histocompatibility B complex. They differ, however, at three independent autosomal loci: Ly-4 and Th-1 determine the surface alloantigens of partly overlapping subsets of T lymphocytes, and Bu-1 determines a surface alloantigen of B lymphocytes. The association of genotypes at these loci with quantitative variation in their ability to regress Rous sarcomas was tested in segregating F4 generation progeny derived from crosses of lines 100 and 63. The Ly-4 and Bu-1 genotypes showed association with Rous sarcoma regression, but the Th-1 genotype did not. Chickens of the Ly-4
a/Ly-4
a, Bu-1
b/Bu-1
b and Ly-4
b/Ly-4
b, Bu-1
a/Bu-1
a genotypes had a significantly higher regressor ability than the other two double homozygous genotypes. These results indicate that higher regression is associated with (1) interaction between the Ly-4 and Bu-1 loci, and (2) complementation between either the line 6 Ly-4
a allele and the line 100 Bu-1
b allele, or the line 100 Ly-4
b allele and the line 6 Bu-1
a allele. 相似文献
14.
15.
Summary Cellular fatty acids inLactobacillus büchneri were transmethylated with H2SO4 catalyst in methanol at elevated temperature. By optimising the reaction time and the amounts of catalyst and methanol used at a fixed temperature it was possible to maximise the lactobacillic acid yield. The yield of lactobacillic acid with this method was better than with the traditional method using base-catalysed saponification followed by HCL-catalysed methylation. 相似文献
16.
Tom M. Spight 《Journal of experimental marine biology and ecology》1973,13(3):215-228
Shell shape, as expressed in terms of log weight/log length, (relative weight), changes progressively as Thais lamellosa Gmelin grows. Relative weight decreases at all sites, but the decrease is relatively rapid at localities with low food supply and correspondingly low growth rates. Snails at these sites are ‘slender’ relative to those at sites with greater barnacle populations. The sitespecific shapes are phenotypic, since snails with fat and with slender parents all became slender in the laboratory where food was readily available and growth rates were higher than those observed at most field localities. Since these snails did not become ‘fat’, food abundance is not the immediately causal, environmental factor promoting a slow change in relative weight. Two other species of Thais live in the same places and undergo similar changes in relative weight. 相似文献
17.
We have used the HLA-C-specific DNA probe pC250 to investigate restriction fragment length polymorphism (RFLP) at the HLA-C locus. Genomic Southern blot hybridization included DNA prepared from a panel of homozygous typing cells representing serological specificities Cw1 to Cw8 and also from samples representing Cw blanks. Although many restriction nucleases failed to reveal any polymorphism, RFLPs were evident with Taq I, Pvu II, Bst XI, Nde 1, and Nci I in addition to the previously reported Eco RI. In the case of Bst XI, a unique RFLP defined a subset of serologically defined Cw blanks. Comparison of RFLP sizes with restriction fragment lengths obtained from the known HLA-Cw3 gene sequence permitted the localization of intragenic C locus RFLLs and the identification of a variable Taq I site in the second intron, a variable Nci I site near the end of the fourth exon, and a variable Pvu lI site in the fifth intron. 相似文献
18.
Four new auxin-responsive RNAs from soybean (Glycine max (L.) Merr., var. Wayne) are described. The RNAs were identified by hybridization to three cDNA probes obtained from a library enriched for sequences which increase in abundance within 60 min after 2,4-D (2,4-dichlorophenoxyacetic acid) treatment. These RNAs appear to define a new class of small (i.e. approximately 550 nucleotides) RNAs that respond extremely rapidly to application of exogenous auxin. In excised elongating hypocotyl sections, an increase in the abundance of these RNAs can be detected 2 to 5 min after treatment with 50 M 2,4-D. This response is half maximal after 10 min and reaches steady state in 60 min. RNA blot analysis shows that these RNAs are expressed differentially in various parts of the seedling. The degree of inducibility by auxin is also organ-specific, with the elongating hypocotyl being the most responsive of the organs tested. The RNAs display identical response specificities with one exception. Accumulation of one RNA, designated 10A, is completely abolished by simultaneous addition of cycloheximide and 2,4-D. This RNA also displays a different 2,4-D dose response than other RNAs examined. These results suggest that more than one mechanism is involved in rapid modulation of gene expression by auxin. 相似文献
19.
20.
Summary Over three years of study, small plants of Cynoglossum officinale consistently produced more flowers per unit of dry weight than large plants. In contrast to earlier results, weight of all seeds tended to increase more than proportional to size. As a result a positive correlation existed between seed set per flower and plant size. The correlation between the mean number of pollinator visits per flower and size was positive but not significant. In a field experiment we found that resources rather than pollen were limiting seed set. Thus, it is unlikely that enhanced pollination of the largest plants causes the size-dependency of seed set per flower. Alternative hypotheses are discussed briefly.Publication of the Meijendel Comité, New Series No. 96 相似文献