Showing papers in "Chemistry & Biology in 2004"

TL;DR: A detailed characterization of the reaction parameters that affect click chemistry-based ABPP is reported and conditions that maximize the speed, sensitivity, and bioorthogonality of this approach are identified.

TL;DR: The crystal structures of the add A- riboswitch and xpt G-riboswitch aptamer modules are reported that distinguish between bound adenine and guanine with exquisite specificity and modulate expression of two different sets of genes.

TL;DR: A screening program for bioactive compounds from marine cyanobacteria led to the isolation of jamaicamides A-C, a novel and highly functionalized lipopeptide containing an alkynyl bromide, vinyl chloride, beta-methoxy eneone system, and pyrrolinone ring, giving insight into the mechanism by which this functional group is created.

TL;DR: It is suggested that interactions with RISC dictate siRNA localization even when siRNA is conjugated to TAT(47-57) peptide, which was distinctly different from nonconjugated free TAT peptide nucleolar localization.

TL;DR: This work has found that E. coli, when incubated with cadmium chloride and sodium sulfide, have the capacity to synthesize intracellular Cadmium sulfide nanocrystals, which are composed of a wurtzite crystal phase with a size distribution of 2-5 nm.

TL;DR: This work provides a single source for those interested in the cellular functions of Cdc25 in cell cycle progression, its role in the progress of cancer and survival of cancer patients, and recent efforts in the design of specific inhibitors.

TL;DR: This system is ideal for whole-cell applications because microarrays present carbohydrate ligands in a manner that mimics interactions at cell-cell interfaces, which allows microarray-based screening of biological samples for contaminants and combinatorial libraries for antiadhesion therapeutics.

TL;DR: The NMR structure of daptomycin indicated that Ca2+ induced a conformational change in d aptomycin that increased its amphipathicity, consistent with the hypothesis that the association of Ca2+, permits it to interact with bacterial membranes with effects that are similar to those of the cationic antimicrobial peptides.

TL;DR: With these microarrays, the binding profiles of five gp120 binding proteins are determined, the carbohydrate structural requirements for these interactions are established, and a potential strategy for HIV vaccine development is identified.

TL;DR: The structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays confirm that the molecules inhibit cell growth by a mechanism dependent on H SP90 inhibition.

TL;DR: Several estrogen-tethered platinum(IV) complexes were prepared and characterized by ESI-MS and (1)H NMR spectroscopy, inspired by the observation that estrogen receptor-positive cells exposed to the hormone are sensitized to cisplatin.

TL;DR: This work presents the first STS crystal structure and identifies, by mutagenic conversion of alfalfa CHS into a functional stilbene synthase, the structural basis for the evolution of STS cyclization specificity in type III polyketide synthase (PKS) enzymes.

TL;DR: Results demonstrate that purmorphamine is a small molecule agonist of Hedgehog signaling, and it may ultimately be useful in the treatment of bone-related disease and neurodegenerative disease.

TL;DR: The results indicate that rifampicin-mediated inhibition of α-synuclein fibrillation and disaggregation of fibrils involves preferential stabilization of monomeric and soluble oligomeric forms, and that r ifampsicin potentially may have therapeutic application for Parkinson's disease.

TL;DR: In this paper, the 8-17 deoxyribozyme was used to identify catalytic DNAs from a common DNA library for the cleavage of all 16 possible dinucleotide junctions.

TL;DR: The authors thank Profs.

TL;DR: Biologically active, therapeutically useful, DNA binding natural products continue to reveal new paradigms for sequence-selective recognition, to enlist beautiful mechanisms of in situ activation for DNA modification, to define new therapeutic targets, to exploit new mechanisms to achieve cellular selectivity, and to provide a rich source of new drugs.

TL;DR: This data indicates that the main proteinase of SARS-CoV, 3CLpro, is an attractive target for therapeutics against SARS owing to its fundamental role in viral replication, and five novel small molecules that show potent inhibitory activity toward 3CL Pro are identified.

TL;DR: It is shown that base pairing at both the 5' and 3' ends of the let-7 binding site, as well as the presence of unpaired RNA residues in the predicted duplexes, are required for lin-41 downregulation.

TL;DR: In concordance with its higher affinity for tumor Hsp90, in vivo PU24FCl accumulates in tumors while being rapidly cleared from normal tissue and leads to single-agent anti-tumor activity at non-toxic doses.

TL;DR: A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140 as discussed by the authors.

TL;DR: The utilization of both taxadiene isomers in the formation of taxa-4(20),11(12)-dien-5alpha-ol is novel, suggesting a reaction mechanism involving promiscuous radical abstraction with selective oxygen insertion rather than epoxidation of the C4,C5-alkene of the natural substrate and allylic rearrangement of the resulting taxa -11( 12)-en-4,5epoxide.

TL;DR: Preliminary data on cells freshly isolated from patients affected by chronic lymphocytic leukemia strongly suggest potential applications of Bcl-2 antagonists as chemosensitizers in cancer therapy.

TL;DR: In this paper, a comprehensive mutational analysis of this structural element and determined the cellular sensitivities of several disease-relevant tyrosine kinases against various inhibitors, such as indolinones and pyrido[2,3-d]pyrimidine inhibitors.

TL;DR: Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients.

TL;DR: Cowpea mosaic virus reagent particles generated by systematic replacement of surface lysines with arginine residues are reported, making it possible to uniquely double label CPMV, expanding its use as an addressable nanoblock.

TL;DR: This study examines the impact of drug-resistant mutations in HIV-1 protease on substrate recognition and demonstrates that most primary active site mutations do not extensively contact substrates, but are critical to inhibitor binding.

TL;DR: Three selected compounds validated to be inhibitors of SARS-CoV Mpro, Hel, and viral entry, respectively, exhibited potent antiviral activity (EC50 < 10 μM) and comparable inhibitory activities in target-specific in vitro assays.

TL;DR: A method to covalently label carrier proteins from PK and NRP synthases using the enzymatic transfer of a modified coenzyme A analog by a 4'-phosphopantetheinyltransferase is described.

TL;DR: Sequence analysis indicates that the macrolide ring of borrelidin is formed by a modular polyketide synthase (PKS) (borA1-A6), a result that was confirmed by disruption ofborA3.