Abstract:
:CD4 functions as a major T-cell surface receptor for human immunodeficiency virus by binding the human immunodeficiency virus type 1 (HIV-1) envelope protein gp120 with relatively high affinity. We have developed constrained aromatically modified analogs of the secondary structures of the first domain of CD4 in order to analyze surfaces involved in binding of gp120. Complementarity determining-like regions (CDRs) of the D1 domain of CD4 were reproduced as synthetic aromatically modified exocyclic (AMEs) forms. The exocyclic CDR3.AME(82-89), derived from the CDR3 (residues 82-89) region of CD4 D1 domain, specifically inhibited binding of recombinant gp120 to both recombinant soluble CD4, and CD4+ Jurkat cells, and blocked syncytium formation and virus particle production caused by HIV-1 infection. We have previously shown that the CDR3.AME analog binds to the CD4 CDR3 region and creates a disabled CD4 heterodimer. We propose that the AME prevents the formation of an essential homodimeric surface needed for efficient HIV binding. Additionally the disabled CD4 receptor may be less able to signal the cell to allow HIV replication and HIV infection. Such compounds may represent a new receptor specific approach to modulate biological functions.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Zhang X,Gaubin M,Briant L,Srikantan V,Murali R,Saragovi U,Weiner D,Devaux C,Autiero M,Piatier-Tonneau D,Greene MIdoi
10.1038/nbt0297-150subject
Has Abstractpub_date
1997-02-01 00:00:00pages
150-4issue
2eissn
1087-0156issn
1546-1696journal_volume
15pub_type
杂志文章abstract::Isolating antigen-specific T lymphocytes is hampered by the low frequency of the cells and the low affinity between T-cell receptors (TCR) and antigen. We describe the isolation and purification of antigen-specific CD8+ T lymphocytes from mixed T-cell populations. Magnetic beads coated with major histocompatibility co...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0398-281
更新日期:1998-03-01 00:00:00
abstract::Expansions of short tandem repeats are genetic variants that have been implicated in several neuropsychiatric and other disorders, but their assessment remains challenging with current polymerase-based methods1-4. Here we introduce a CRISPR-Cas-based enrichment strategy for nanopore sequencing combined with an algorit...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0293-x
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abstract::Noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer-associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencin...
journal_title:Nature biotechnology
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更新日期:2011-07-31 00:00:00
abstract::Technologies that enable targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we describe a programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fuse...
journal_title:Nature biotechnology
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abstract::Pollen-mediated movement of transgenes from transplastomic oilseed rape (Brassica napus) into wild relatives will be avoided if chloroplasts are maternally transmitted. We assess the probability of chloroplast exchange between conventional oilseed rape and wild Brassica rapa to model the future behavior of transplasto...
journal_title:Nature biotechnology
pub_type: 杂志文章
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更新日期:1999-04-01 00:00:00
abstract::Efficient delivery of small interfering (si)RNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll-like receptor (TLR)9 targets and silences genes in TLR9(+) myeloid cells and B ...
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abstract::Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor ...
journal_title:Nature biotechnology
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更新日期:2009-02-01 00:00:00
abstract::DNA delivery of tumor antigens can activate specific immune attack on cancer cells. However, antigens may be weak, and immune capacity can be compromised. Fusion of genes encoding activating sequences to the tumor antigen sequence facilitates promotion and manipulation of effector pathways. Idiotypic determinants of B...
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pub_type: 杂志文章
doi:10.1038/90816
更新日期:2001-08-01 00:00:00
abstract::To select for bacterial strains with enhanced phenotypes, random fragments of a whole genome, or a defined region of the genome, are cloned in a nonreplicating vector. The resulting plasmids are integrated by recombination into the homologous DNA region of the original strain. Integration gives rise to a nontandem dir...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0697-564
更新日期:1997-06-01 00:00:00
abstract::Can weakly active phytochemicals be combined synergistically to produce new antibacterial treatments? ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1206-1504
更新日期:2006-12-01 00:00:00
abstract::The ability to detect single protein molecules in blood could accelerate the discovery and use of more sensitive diagnostic biomarkers. To detect low-abundance proteins in blood, we captured them on microscopic beads decorated with specific antibodies and then labeled the immunocomplexes (one or zero labeled target pr...
journal_title:Nature biotechnology
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doi:10.1038/nbt.1641
更新日期:2010-06-01 00:00:00
abstract::The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible si...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2108
更新日期:2012-01-22 00:00:00
abstract::Through sequential generations of random mutagenesis and screening, we have directed the evolution of an esterase for deprotection of an antibiotic p-nitrobenzyl ester in aqueous-organic solvents. Because rapid screening directly on the desired antibiotic (loracarbef) nucleus p-nitrobenzyl ester was not feasible, the ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0496-458
更新日期:1996-04-01 00:00:00
abstract::Plant satellite RNAs generally reduce the level of helper virus accumulation and attenuate the disease symptoms induced by the helper virus that they depend upon for replication and packaging. As such, satellite RNAs could be used as biocontrol agents to reduce the level of disease in field crops, either by the applic...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1096-1264
更新日期:1996-10-01 00:00:00
abstract::Selectable marker genes are required to ensure the efficient genetic modification of crops. Economic incentives and safety concerns have prompted the development of several strategies (site-specific recombination, homologous recombination, transposition, and co-transformation) to eliminate these genes from the genome ...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0602-575
更新日期:2002-06-01 00:00:00
abstract::Efficiently generating evidence of clinical utility is a major challenge for ensuring clinical adoption of valuable diagnostics. A new approach to reimbursement in the United States offers a balance between evidence and incentives for molecular diagnostic tests. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1110-1157
更新日期:2010-11-01 00:00:00
abstract::By using an engineered, self-assembling, proteinaceous, 2-nm pore equipped with a metal-actuated switch, a technique to reversibly permeabilize the plasma membrane to small molecules (approximately 1000 Da) has been developed. We have demonstrated the dose-dependent permeabilization of fibroblasts by pores designed to...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0397-278
更新日期:1997-03-01 00:00:00
abstract::Whole-genome mRNA quantitation can be used to identify the genes that are most responsive to environmental or genotypic change. By searching for mutually similar DNA elements among the upstream non-coding DNA sequences of these genes, we can identify candidate regulatory motifs and corresponding candidate sets of core...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1098-939
更新日期:1998-10-01 00:00:00
abstract::The nonprofit Pew Initiative on Food and Biotechnology is closing, but the need for an independent and neutral body to facilitate dialog on US biotech policy has never been greater. ...
journal_title:Nature biotechnology
pub_type: 社论
doi:10.1038/nbt0207-143
更新日期:2007-02-01 00:00:00
abstract::We describe a novel approach to design a set of primers selective for large groups of genes. This method is based on the distribution frequency of all nucleotide combinations (octa- to decanucleotides), and the combined ability of primer pairs, based on these oligonucleotides, to detect genes. By analyzing 1000 human ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0796-857
更新日期:1996-07-01 00:00:00
abstract::Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14...
journal_title:Nature biotechnology
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doi:10.1038/s41587-019-0037-y
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abstract::Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and consistently identified fo...
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更新日期:2007-01-01 00:00:00
abstract::The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two ...
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更新日期:2005-12-01 00:00:00
abstract::Nucleotide variants, especially those related to epigenetic functions, provide critical regulatory information beyond simple genomic sequence, and they define cell status in higher organisms. 5-Methylcytosine, which is found in DNA, was until recently the only nucleotide variant studied in terms of epigenetics in euka...
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更新日期:2012-11-01 00:00:00
abstract::We have evaluated inhibition of the plasmid-born chloramphenicol acetyl transferase gene (CAT) by the hammerhead ribozyme and antisense RNA in Escherichia coli where the translation and transcription rates have been modified. Whereas neither antisense nor the hammerhead had an inhibitory effect on CAT activity in wild...
journal_title:Nature biotechnology
pub_type: 杂志文章
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更新日期:1997-05-01 00:00:00
abstract::DNA microarrays have the ability to analyze the expression of thousands of the same set of genes under at least two different experimental conditions. However, DNA microarrays require substantial amounts of RNA to generate the probes, especially when bacterial RNA is used for hybridization (50 microg of bacterial tota...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/76543
更新日期:2000-06-01 00:00:00
abstract::Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4047
更新日期:2018-02-01 00:00:00
abstract::We used the integrase from phage phiC31 to integrate the human Factor IX (hFIX) gene permanently into specific sites in the mouse genome. A plasmid containing attB and an expression cassette for hFIX was delivered to the livers of mice by using high-pressure tail vein injection. When an integrase expression plasmid wa...
journal_title:Nature biotechnology
pub_type: 杂志文章
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更新日期:2002-11-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease of unknown etiology that affects many organs, including the kidney. The presence of multiple autoantibodies and other immunological abnormalities point to basic defects in immunoregulatory controls that normally maintain self-tolerance. T...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/77296
更新日期:2000-07-01 00:00:00
abstract::We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes...
journal_title:Nature biotechnology
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更新日期:2011-12-25 00:00:00