Abstract:
:Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.
journal_name
Proc Natl Acad Sci U S Aauthors
Dickinson LA,Gulizia RJ,Trauger JW,Baird EE,Mosier DE,Gottesfeld JM,Dervan PBdoi
10.1073/pnas.95.22.12890subject
Has Abstractpub_date
1998-10-27 00:00:00pages
12890-5issue
22eissn
0027-8424issn
1091-6490journal_volume
95pub_type
杂志文章abstract::Maize domestication is one of the greatest feats of artificial selection and evolution, wherein a weedy plant in Central Mexico was converted through human-mediated selection into the most productive crop in the world. In fact, the changes were so astounding that it took much of the last century to identify modern mai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.0901122106
更新日期:2009-06-16 00:00:00
abstract::Poliovirus mRNA and mRNA transcribed from vesicular stomatitis virus and reovirus genomes efficiently direct protein synthesis in vivo under experimental conditions where the initiation of host protein synthesis is selectively blocked. The selective blockage of host peptide chain initiation after exposure to hypertoni...
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.72.4.1258
更新日期:1975-04-01 00:00:00
abstract::We report the in vitro long-term (20 wk) changes in cells exposed to well-characterized gold nanoparticles (Au NPs) with varying shapes and surface coatings under both chronic (exposure to Au NPs continuously over 20 wk) and nonchronic (initial acute cell exposure to Au NPs, followed by 20 wk in NP-free cell media) co...
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.1616400113
更新日期:2016-11-22 00:00:00
abstract::The planarity of peptide bonds is an assumption that underlies decades of theoretical modeling of proteins. Peptide bonds strongly deviating from planarity are considered very rare features of protein structure that occur for functional reasons. Here, empirical analyses of atomic-resolution protein structures reveal t...
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.1107115108
更新日期:2012-01-10 00:00:00
abstract::G protein-coupled receptors mediate biological signals by stimulating nucleotide exchange in heterotrimeric G proteins (Galphabetagamma). Receptor dimers have been proposed as the functional unit responsible for catalytic interaction with Galphabetagamma. To investigate whether a G protein-coupled receptor monomer can...
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.0701967104
更新日期:2007-06-26 00:00:00
abstract::The process by which cells select one of several specific programs of genetic information in development was examined in homoeotic mutant Antennapedia of Rappaport in Drosophila melanogaster. The results show that the alteration of determination from antenna to leg induced by this homoeotic mutation occurs in a popula...
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.64.1.176
更新日期:1969-09-01 00:00:00
abstract::Time-resolved optical measurements encompassing the femtoseconds to seconds time scales have been used to investigate Rhodobacter capsulatus reaction centers (RCs) in which the histidine residue at position 200 on the M polypeptide has been changed to a leucine by site-directed mutagenesis. The HisM200----Leu RC, whic...
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.85.20.7562
更新日期:1988-10-01 00:00:00
abstract::The impossibility theorems that abound in the theory of social choice show that there can be no satisfactory method for electing and ranking in the context of the traditional, 700-year-old model. A more realistic model, whose antecedents may be traced to Laplace and Galton, leads to a new theory that avoids all imposs...
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.0702634104
更新日期:2007-05-22 00:00:00
abstract::The determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorou...
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.0506412103
更新日期:2006-02-07 00:00:00
abstract::Remarkable progress has come from whole-brain models linking anatomy and function. Paradoxically, it is not clear how a neuronal dynamical system running in the fixed human anatomical connectome can give rise to the rich changes in the functional repertoire associated with human brain function, which is impossible to ...
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.1921475117
更新日期:2020-04-28 00:00:00
abstract::A variety of agricultural plant species, including corn, respond to insect herbivore damage by releasing large quantities of volatile compounds and, as a result, become highly attractive to parasitic wasps that attack the herbivores. An elicitor of plant volatiles, N-(17-hydroxylinolenoyl)-L-glutamine, named volicitin...
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.95.23.13971
更新日期:1998-11-10 00:00:00
abstract::The migration of species across interfaces can crucially affect the performance of heterogeneous catalysts. A key concept in using bimetallic catalysts for hydrogenation is that the active metal supplies hydrogen atoms to the host metal, where selective hydrogenation can then occur. Herein, we demonstrate that, follow...
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.2010413117
更新日期:2020-09-15 00:00:00
abstract::Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that acco...
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.1620508114
更新日期:2017-03-21 00:00:00
abstract::Tetrodotoxin was infused into the suprachiasmatic nuclei of unanesthetized and unrestrained rats continuously for 14 days. The internal timekeeping mechanism of the circadian pacemaker in the nuclei continued to oscillate unaffected by this treatment, although the toxin reversibly blocked function of both the input pa...
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.84.6.1694
更新日期:1987-03-01 00:00:00
abstract::Circadian rhythms in metazoan eukaryotes are controlled by an endogenous molecular clock. It functions in many locations, including subsets of brain neurons (clock neurons) within the central nervous system. Although the molecular clock relies on transcription/translation feedback loops, posttranscriptional regulation...
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.1605837113
更新日期:2016-05-24 00:00:00
abstract::By using a systematic genetic approach, the resonances in the 19F NMR spectrum of 3-fluorotyrosine-substituted lac repressor protein have been assigned. The NMR data indicate that each monomer of the repressor consists of two distinct and independent domains. One domain, the NH2-terminal sixth of the primary sequence,...
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.78.5.2707
更新日期:1981-05-01 00:00:00
abstract::The derivation of germ-line competent avian primordial germ cells establishes a cell-based model system for the investigation of germ cell differentiation and the production of genetically modified animals. Current methods to modify primordial germ cells using DNA or retroviral vectors are inefficient and prone to epi...
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.1118715109
更新日期:2012-06-05 00:00:00
abstract::Unlike other cation channels, each subunit of most transient receptor potential (TRP) channels has an additional TRP-domain helix with an invariant tryptophan immediately trailing the gate-bearing S6. Recent cryo-electron microscopy of TRP vanilloid subfamily, member 1 structures revealed that this domain is a five-tu...
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.1502366112
更新日期:2015-03-17 00:00:00
abstract::Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyc...
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.75.4.1788
更新日期:1978-04-01 00:00:00
abstract::Studies of replicative and chronological lifespan in Saccharomyces cerevisiae have advanced understanding of longevity in all eukaryotes. Chronological lifespan in this species is defined as the age-dependent viability of nondividing cells. To date this parameter has only been estimated under calorie restriction, mimi...
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.1323918111
更新日期:2014-04-15 00:00:00
abstract::Novel antibiotics are urgently needed to combat multidrug-resistant pathogens. Venoms represent previously untapped sources of novel drugs. Here we repurposed mastoparan-L, the toxic active principle derived from the venom of the wasp Vespula lewisii, into synthetic antimicrobials. We engineered within its N terminus ...
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.2012379117
更新日期:2020-10-27 00:00:00
abstract::The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell cul...
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.0806308105
更新日期:2008-09-02 00:00:00
abstract::Agrobacterium tumefaciens is routinely used to engineer desirable genes into dicotyledonous plants. However, the economically important graminaceous plant maize is refractory to tumor induction by inoculation with virulent strains of A. tumefaciens. Currently, the only clearcut evidence for transferred DNA (T-DNA) tra...
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.90.4.1488
更新日期:1993-02-15 00:00:00
abstract::Tomato plants overexpressing a prosystemin gene that encodes the precursor of a mobile wound signal called systemin have been shown previously to constitutively synthesize extraordinarily high levels of two defensive proteinase inhibitor proteins in leaves in the absence of wounding. We herein report that leaves of th...
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.92.2.407
更新日期:1995-01-17 00:00:00
abstract::Addition of antisense oligonucleotides to cell cultures has been used to specifically inhibit gene expression. We have investigated the mechanism by which oligonucleotides enter living cells. These compounds are taken up by cells in a saturable, size-dependent manner compatible with receptor-mediated endocytosis. Poly...
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.86.10.3474
更新日期:1989-05-01 00:00:00
abstract::A promising strategy for DNA sequencing exploits transposons to provide mobile sites for the binding of sequencing primers. For such a strategy to be maximally efficient, the location and orientation of the transposon must be readily determined and the insertion sites should be randomly distributed. We demonstrate an ...
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.87.16.6213
更新日期:1990-08-01 00:00:00
abstract::We constructed a comprehensive cDNA library from HeLa cell mRNA in a vector that directs expression of the cDNA in Saccharomyces cerevisiae. We used this library to clone the human counterpart of the Sa. cerevisiae CCAAT-binding transcription factor, Hap2, by functional complementation of a hap2 mutation. The cDNA enc...
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.88.5.1968
更新日期:1991-03-01 00:00:00
abstract::Many aspects of plant development, including patterning and tropisms, are largely dependent on the asymmetric distribution of the plant signaling molecule auxin. Auxin transport inhibitors (ATIs), which interfere with directional auxin transport, have been essential tools in formulating this concept. However, despite ...
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.0711414105
更新日期:2008-03-18 00:00:00
abstract::Hepatocytes polarize by forming functionally distinct sinusoidal (basolateral) and canalicular (apical) plasma membrane domains. Two distinct routes are used for delivery of membrane proteins to the canaliculus. Proteins having glycosylphosphatidylinositol anchors or single transmembrane domains are targeted to the si...
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.0503702102
更新日期:2005-10-18 00:00:00
abstract::Protein framework alterations in heritable Cu, Zn superoxide dismutase (SOD) mutants cause misassembly and aggregation in cells affected by the motor neuron disease ALS. However, the mechanistic relationship between superoxide dismutase 1 (SOD1) mutations and human disease is controversial, with many hypotheses postul...
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.1308531111
更新日期:2014-10-28 00:00:00