Abstract:
:Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.
journal_name
Proc Natl Acad Sci U S Aauthors
Kelly JJ,Baird EE,Dervan PBdoi
10.1073/pnas.93.14.6981subject
Has Abstractpub_date
1996-07-09 00:00:00pages
6981-5issue
14eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::We report the results of crystallographic difference maps at 3.0-A resolution of complexes of metal-nucleoside triphosphates with aspartate carbamoyltransferase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) from Escherichia coli. The complexes Gd3+-ATP, Al3+-ATP, and Gd3+-CTP bind to the allosteric...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.23.7171
更新日期:1982-12-01 00:00:00
abstract::The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial va...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.2.1209
更新日期:1980-02-01 00:00:00
abstract::Clinically available drugs active against Epstein-Barr virus (EBV) and other human herpesviruses are limited to those targeting viral DNA replication. To identify compounds directed against other steps in the viral life cycle, we searched for drugs active against the EBV SM protein, which is essential for infectious v...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1523686113
更新日期:2016-03-29 00:00:00
abstract::During heat shock, structural changes in proteins and membranes may lead to cell death. While GroE and other chaperone proteins are involved in the prevention of stress-induced protein aggregation and in the recovery of protein structures, a mechanism for short-term membrane stabilization during stress remains to be e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.6.2192
更新日期:1997-03-18 00:00:00
abstract::The thymus provides multiple microenvironments that are essential for the development and repertoire selection of T lymphocytes. The thymic cortex induces the generation and positive selection of T lymphocytes, whereas the thymic medulla establishes self-tolerance among the positively selected T lymphocytes. Cortical ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1301799110
更新日期:2013-06-11 00:00:00
abstract::Idiopathic interstitial pneumonias (IIPs) have a progressive and often fatal course, and their enigmatic etiology has complicated approaches to effective therapies. Idiopathic pulmonary fibrosis (IPF) is the most common of IIPs and shares with IIPs an increased incidence with age and unexplained scarring in the lung. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804280105
更新日期:2008-09-02 00:00:00
abstract::Murine mucopolysaccharidosis type VII is a heritable disease caused by a spontaneous mutation, gus(mps), closely linked to the beta-glucuronidase structural gene on chromosome 5. Mice homozygous for the mutation have a > 200-fold decrease in beta-glucuronidase mRNA levels and virtually no enzyme activity detectable by...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.14.6567
更新日期:1993-07-15 00:00:00
abstract::Understanding how institutional changes within academia may affect the overall potential of science requires a better quantitative representation of how careers evolve over time. Because knowledge spillovers, cumulative advantage, competition, and collaboration are distinctive features of the academic profession, both...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1121429109
更新日期:2012-04-03 00:00:00
abstract::The scaling of respiratory metabolism with body mass is one of the most pervasive phenomena in biology. Using a single allometric equation to characterize empirical scaling relationships and to evaluate alternative hypotheses about mechanisms has been controversial. We developed a method to directly measure respiratio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0902554107
更新日期:2010-01-26 00:00:00
abstract::Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue gene HFE has been found to be a primary cause of HH. However, many individuals homozygous for the defective allele of HFE do not deve...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.091088998
更新日期:2001-04-24 00:00:00
abstract::The matrix-2 (M2) protein from influenza A virus is a tetrameric, integral transmembrane (TM) protein that plays a vital role in viral replication by proton flux into the virus. The His37 tetrad is a pH sensor in the center of the M2 TM helix that activates the channel in response to the low endosomal pH. M2 consists ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1913385117
更新日期:2020-02-18 00:00:00
abstract::ErbB3 (HER3) is a member of the EGF receptor (EGFR) family of receptor tyrosine kinases, which, unlike the other three family members, contains a pseudo kinase in place of a tyrosine kinase domain. In cancer, ErbB3 activation is driven by a ligand-dependent mechanism through the formation of heterodimers with EGFR, Er...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1518361112
更新日期:2015-10-27 00:00:00
abstract::Sequence-specific gene silencing by short hairpin (sh) RNAs has recently emerged as an indispensable tool for understanding gene function and a promising avenue for drug discovery. However, a wider biomedical use of this approach is hindered by the lack of straightforward methods for achieving uniform expression of sh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1103532108
更新日期:2011-08-02 00:00:00
abstract::Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inevitable in metastatic EGFR-mutant lung cancers. Here, we modeled disease progression using EGFR-mutant human tumor cell lines. Although five of six models displayed alterations already found in humans, one harbored an unexpected seconda...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1203530109
更新日期:2012-07-31 00:00:00
abstract::Hatchlings of the painted turtle (Chrysemys picta marginata) are unique as the only reptile and highest vertebrate life form known to tolerate the natural freezing of extracellular body fluids during winter hibernation. Turtles survived frequent exposures to temperatures as low as -6 degrees C to -8 degrees C in their...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.21.8350
更新日期:1988-11-01 00:00:00
abstract::Misfolded proteins are an emerging hallmark of cardiac diseases. Although some misfolded proteins, such as desmin, are associated with mutations in the genes encoding these disease-associated proteins, little is known regarding more general mechanisms that contribute to the generation of misfolded proteins in the hear...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1420196111
更新日期:2014-12-09 00:00:00
abstract::New neurons are continuously generated in restricted regions of the adult mammalian brain. Although these adult-born neurons have been shown to receive synaptic inputs, little is known about their synaptic outputs. Using retrovirus-mediated birth-dating and labeling in combination with serial section electron microsco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0806658105
更新日期:2008-09-16 00:00:00
abstract::The ubiquitin ligase Siah2 has been shown to regulate prolyl hydroxylase 3 (PHD3) stability with concomitant effect on HIF-1alpha availability. Because HIF-1alpha is implicated in tumorigenesis and metastasis, we used SW1 mouse melanoma cells, which develop primary tumors with a propensity to metastasize, in a syngene...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804063105
更新日期:2008-10-28 00:00:00
abstract::Transmission electron microscopy studies have been used to argue that magnetite crystals in carbonate from Martian meteorite ALH84001 have a composition and morphology indistinguishable from that of magnetotactic bacteria. It has even been claimed from scanning electron microscopy imaging that some ALH84001 magnetite ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402292101
更新日期:2004-06-01 00:00:00
abstract::Energy transfer is enhanced by translational diffusion of the donor and acceptor [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the sum of the diffusion coefficients of the donor and acceptor, tau(0) is the life...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.12.5746
更新日期:1978-12-01 00:00:00
abstract::It has been a long-sought goal of quantum simulation to find answers to outstanding questions in condensed-matter physics. A famous example is finding the ground state and the excitations of the two-dimensional (2D) Hubbard model with strong repulsion below half-filling. This system is a doped antiferromagnet and is o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2004268117
更新日期:2020-10-20 00:00:00
abstract::Tramadol, previously only known as a synthetic analgesic, has now been found in the bark and wood of roots of the African medicinal tree Nauclea latifolia. At present, no direct evidence is available as to the biosynthetic pathway of its unusual skeleton. To provide guidance as to possible biosynthetic precursors, we ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1506011112
更新日期:2015-07-07 00:00:00
abstract::We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N-acetylatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.4.1597
更新日期:1999-02-16 00:00:00
abstract::Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of (125)I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab')(2) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.9.4209
更新日期:1978-09-01 00:00:00
abstract::The two internal transcribed spacers (ITS1 and ITS2) of rDNA of three members of the Ixodes ricinus "complex" (Acari: Ixodidae) were sequenced. Sequence variation was assessed for the North American species I. scapularis, I. dammini, and I. pacificus at three levels: within individual/population, between individuals o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.21.10221
更新日期:1993-11-01 00:00:00
abstract::The switch from membrane-bound to secreted IgM is accomplished by producing alternative forms of mRNA from a single mu heavy-chain gene. This process might be controlled at any of three steps--transcription termination, RNA splicing, or RNA cleavage/poly(A) addition. To distinguish between these possibilities, we have...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.24.8658
更新日期:1985-12-01 00:00:00
abstract::Strongylocentrotus intermedius (A. Agassiz, 1863) is an economically important sea urchin inhabiting the northwest Pacific region of Asia. The northern Primorye (Sea of Japan) populations of S. intermedius consist of two sympatric morphological forms, "usual" (U) and "gray" (G). The two forms are significantly differe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0807860105
更新日期:2008-10-21 00:00:00
abstract::Targeted gene disruption in the murine TOP3beta gene-encoding DNA topoisomerase IIIbeta was carried out. In contrast to the embryonic lethality of mutant mice lacking DNA topoisomerase IIIalpha, top3beta(-/-) nulls are viable and grow to maturity with no apparent defects. Mice lacking DNA topoisomerase IIIbeta have a ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.101132498
更新日期:2001-05-08 00:00:00
abstract::[3H]Forskolin bound to high- and low-affinity sites in the rat brain. The high-affinity site was discretely located, with highest densities in the striatum, nucleus accumbens, olfactory tubercule, substantia nigra, hippocampus, and the molecular layers of the cerebellum. This site did not correlate well with the distr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.9.3216
更新日期:1988-05-01 00:00:00
abstract::Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.4.1805
更新日期:1978-04-01 00:00:00