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排序方式: 共有395条查询结果,搜索用时 281 毫秒
81.
Alexander J. Bridges Donna R. Cody Hairong Zhou Amy McMichael David W. Fry 《Bioorganic & medicinal chemistry》1995,3(12)
4-Benzylaminoquinazolines can be potent reversible inhibitors of the EGFR tyrosine kinase at the ATP binding site. Examination of benzylic methylation reveals that an (R)-methyl group is four- to six-fold activating, with an optimal Ki of 630 pM for compound II. In sharp contrast, (S)-methylation causes a > 30 to 500-fold loss of inhibitory activity, showing that the ATP-binding site of the receptor has very low tolerance for even moderate out-of-plane bulk in certain directions. It is suggested that the best of these inhibitors can induce a conformation of the kinase not available to poorer inhibitors. 相似文献
82.
83.
A. J. McMichael Jennifer M. Phillips A. R. Williamson Thereza Imanishi O. Mäkelä 《Immunogenetics》1975,2(1):161-173
The primary anti-NP response in C57BL/6 and CBA mice was analyzed by isoelectric focusing. Antibody responses in C57 mice were restricted in heterogeneity and over 80 % of this strain shared an isoelectric focusing spectrum characteristic of an homogeneous antibody (spectrotype). This spectrotype N-l was inherited as a dominant characteristic in (CBA×C57)F1 mice, and backcross analysis revealed that it was genetically linked to the heavy chain allotypeIg-1
b
. It thus behaved as a marker similar to the fine specificity characteristic of heteroclitic antibody. Elution studies showed that antibody with the spectrotype N-1 was heteroclitic, with a higher affinity for NIP and NNP than for the immunogen NP. It is argued that a) a single germ-lineV gene (designated N-1) codes for the VH region of this antibody and b) in C57BL/6 mice this geneV
H
N-1 is closely linked toIg-1
b
.Abbreviations BSA
bovine serum albumin
- CG
Chicken globulin
- NP
(4-Hydroxy-3-nitrophenyl)acetyl
- NIP
(4-Hydroxy-5-iodo-3-nitrophenyl)acetyl
- NBrP
(4 Hydroxy-5-bromo-3-nitrophenyl)acetyl
- NNP
(4-Hydroxy-3,5-dinitrophenyl)acetyl
- NIP-Cap
NIP-aminocaproate
- I50
Hapten concentration causing 50% inhibition of antigen binding
- SRC
Sheep red cells
- IEF
Isoelectric focusing
- PBS
Phosphate buffered saline, pH 7.4 相似文献
84.
85.
Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution 总被引:1,自引:0,他引:1
Lemur beta-related globin genes have been isolated and sequenced. Orthology
of prosimian and human epsilon-, gamma-, and beta-related globin genes was
established by dot-matrix analysis. All of these lemur globin genes
potentially encode functional beta-related globin polypeptides, though
precisely when the gamma-globin gene is expressed remains unknown. The
organization of the 18-kb brown lemur beta-globin gene cluster (5'
epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by
contraction via unequal crossing-over from the putative ancestral mammalian
beta-globin gene cluster (5' epsilon-gamma- eta-delta-beta 3'). The dwarf
lemur nonadult globin genes are arranged as in the brown lemur. Similar
levels of synonymous (silent) nucleotide substitutions and noncoding DNA
sequence differences have accumulated between species in all of these
genes, suggesting a uniform rate of noncoding DNA divergence throughout
primate beta-globin gene clusters. These differences are comparable with
those observed in the nonfunctional psi eta pseudogene and have therefore
accumulated at the presumably maximal neutral rate. In contrast,
nonsynonymous (replacement) nucleotide substitutions show a significant
heterogeneity in distribution for both the same gene in different lineages
and different genes in the same lineage. These major fluctuations in
replacement but not silent substitution rates cannot be attributed to
changes in mutation rate, suggesting that changes in the rate of globin
polypeptide evolution in primates is not governed solely by variable
mutation rates.
相似文献
86.
87.
C E Allsopp R M Harding C Taylor M Bunce D Kwiatkowski N Anstey D Brewster A J McMichael B M Greenwood A V Hill 《American journal of human genetics》1992,50(2):411-421
A total of 752 individuals from The Gambia, west Africa who are representative of the major ethnic groups in the capital, Banjul, were serologically typed for HLA-A, -B, and -C antigens. Although all were typically "African" in their antigenic profiles, some marked frequency differences were found between the ethnic groups. Genetic distance comparisons with several other African populations showed that, although these west African populations clustered closely together, the positions of the various ethnic groups in The Gambia were consistent with historical and linguistic evidence of their affinities with one another and with other African populations. Despite the potential confounding effects both of selection by infectious diseases and of genetic drift caused by local differences in population structure, HLA frequencies appear to be of value in measuring inter- and intraregional population affinities in sub-Saharan Africa. 相似文献
88.
L cells expressing either the A/NT/60/68 nucleoprotein or the A/PR/8/34 (H1) hemagglutinin by DNA mediated gene transfer were used to investigate recognition by influenza A specific cytotoxic T lymphocytes (CTL). A subpopulation of CTL that recognized the H1 hemagglutinin was detected in mice primed with either A/PR/8/34 (H1N1) or A/JAP/305/57 (H2N2) influenza viruses. However, neither CTL from mice primed with A/NT/60/68 (H3N2) nor the recombinant virus X31 (H3N2) showed any activity on L cells expressing H1. These results showed that the majority of fully crossreactive CTL do not recognize the hemagglutinin molecule. A comparison between nucleoprotein and hemagglutinin transfected L cells reveals the nucleoprotein as the major target for CTL that are crossreactive on the three pandemic strains of human influenza A virus. 相似文献
89.
90.
The operation of clonal selection for cells of the B-lymphocyte line is discussed with regard to: 1) The clonal repertoire determined by antigen binding to B lymphocytes, which is much larger than that determined by limiting dilution cloning assays. This quantitative difference is interpreted in terms of the multiple shared specificities of each antibody molecule. 2) Multiclonal responses and initial selection by antigen of particular clones (preferential primary selection). 3) Clonal dominance. During an immune response one clone (or a small number of clones) of B cells is preferentially selected and proliferated, apparently at random, from a heterogeneous population of cells capable of responding to the given antigen. Co-dominance of two or more clones simultaneously can be obtained by mixing selected clones. Secreted antibody is seen as playing a role in the establishment of clonal dominance. A model for clonal expansion is presented. The model attempts to explain the generation of memory and antibody secreting cells within each clonal expansion in terms of the ratio of two signals, one for proliferation and one for differentiation. The delivery of these signals is proposed to involve the receptor antibody-antigen interaction for proliferation and a self-recognition site interaction for differentiation. 相似文献