PubMed Journal Database | ACS chemical biology 
The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 21 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and books. BioPortfolio aims to publish relevant information on published papers, clinical trials and news associated with users selected topics.
For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.
Showing PubMed Articles 1–25 of 221 from ACS chemical biology
Evidence for Age-Dependent in Vivo Conformational Rearrangement within Aβ Amyloid Deposits.
Deposition of aggregated Aβ peptide in the brain is one of the major hallmarks of Alzheimer's disease. Using a combination of two structurally different, but related, hypersensitive fluorescent amyloid markers, LCOs, reporting on separate ultrastructural elements, we show that conformational rearrangement occurs within Aβ plaques of transgenic mouse models as the animals age. This important mechanistic insight should aid the design and evaluation of experiments currently using plaque load as readout.
Chemical Interrogation of the Neuronal Kinome Using a Primary Cell-Based Screening Assay.
A fundamental impediment to functional recovery from spinal cord injury (SCI) and traumatic brain injury is the lack of sufficient axonal regeneration in the adult central nervous system. There is thus a need to develop agents that can stimulate axon growth to re-establish severed connections. Given the critical role played by protein kinases in regulating axon growth and the potential for pharmacological intervention, small molecule protein kinase inhibitors present a promising therapeutic strategy. Here,...
Reporter enzyme inhibitor study to aid assembly of orthogonal reporter gene assays.
Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investigated eight reporter enzymes differing in brightness, emission spectrum, stability, and substrate requirements. These included common reporter enzymes such as firefly luciferase (Photinus pyrali...
Dendritic cell (DC)-based vaccines have shown promise as an immunotherapeutic modality for cancer and infectious diseases in many preclinical studies and clinical trials. Provenge (sipuleucel-T), a DC-based vaccine based on ex vivo-generated autologous DCs loaded with antigens, has recently received FDA approval for prostate cancer treatment, further validating the potential of DC-based vaccine modalities. However, direct antigen delivery to DCs in vivo via DC-specific surface receptors would enable a more...
Synthetic Molecular Evolution of Pore-Forming Peptides by Iterative Combinatorial Library Screening.
We previously reported the de novo design of a combinatorial peptide library that was subjected to high-throughput screening to identify membrane-permeabilizing antimicrobial peptides that have β-sheet-like secondary structure. Those peptides do not form discrete pores in membranes but instead partition into membrane interfaces and cause transient permeabilization by membrane disruption, but only when present at high concentration. In this work, we used a consensus sequence from that initial screen as a te...
RNA "Traffic Lights": An Analytical Tool to Monitor siRNA Integrity.
The combination of thiazole orange and thiazole red as an internal energy transfer-based fluorophore pair in oligonucleotides provides an outstanding analytical tool to follow DNA/RNA hybridization through a distinct fluorescence color change from red to green. Herein, we demonstrate that this concept can be applied to small interfering RNA (siRNA) to monitor RNA integrity in living cells in real time with a remarkable dynamic range and excellent contrast ratios in cellular media. Furthermore, we show that...
We report 12 cyanobactin cyclic peptides, the aestuaramides, from the cultivated cyanobacterium Lyngbya aestuarii. We show that aestuaramides are synthesized enzymatically as reverse O-prenylated tyrosine ethers that subsequently undergo a Claisen rearrangement to produce forward C-prenylated tyrosine. These results reveal that a non-enzymatic Claisen rearrangement dictates isoprene regiochemistry in a natural system. They also reveal one of the mechanisms that organisms use to generate structurally diverse...
ADARs (adenosine deaminases acting on RNA) are RNA editing enzymes that bind double helical RNAs and deaminate select adenosines (A). The product inosine (I) is read during translation as guanosine (G) so such changes can alter codon meaning. ADAR-catalyzed A to I changes occur in coding sequences for several proteins of importance to the nervous system. However, these sites constitute only a very small fraction of known A to I sites in the human transcriptome and the significance of editing at the vast maj...
Through microbial engineering, biosynthesis has the potential to produce thousands of chemicals used in everyday life. Metabolic engineering and synthetic biology are fields driven by the manipulation of genes, genetic regulatory systems, and enzymatic pathways for developing highly productive microbial strains. Fundamentally, it is the biochemical characteristics of the enzymes themselves that dictate flux through a biosynthetic pathway towards the product of interest. As metabolic engineers target sophist...
Fat chance! Getting a grip on a slippery modification.
Protein palmitoylation describes the post-translational fatty acyl thioesterification of cellular cysteine residues and is critical for the localization, trafficking, and compartmentalization of a large number of membrane proteins. This labile thioester modification facilitates a dynamic acylation cycle that directionally traffics key signaling complexes, receptors, and channels to select membrane compartments. Chemical enrichment and advanced mass spectrometry-based proteomics methods have highlighted a pe...
The modulation of kinase function has become an important goal in modern drug discovery and chemical biology research. In cancer-targeted therapies, kinase inhibitors have been experiencing an upsurge, which can be measured by the increasing number of kinase inhibitors approved by the FDA in recent years. However, lack of efficacy, limited selectivity, and the emergence of acquired drug resistance still represent major bottlenecks in the clinic and challenge inhibitor development. Most known kinase inhibito...
Drugging topoisomerases: lessons and challenges.
Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication, and topoisomerase inhibitors are among the most effective and most commonly used anticancer and antibacterial drugs. This review consists of two parts. In the first part ("Lessons"), it gives background information on the catalytic mechanisms of the different enzyme families (6 different genes in humans and 4 in most bacteria), describes the "interfacial inhibition"...
Transition States, analogues, and drug development.
Enzymes achieve their transition states by dynamic conformational searches on the femtosecond to picosecond time scale. Mimics of reactants at enzymatic transition states bind tightly to enzymes by stabilizing the conformation optimized through evolution for transition state formation. Instead of forming the transient transition state geometry, transition state analogues convert the short-lived transition state to a stable thermodynamic state. Enzymatic transition states are understood by combining kinetic...
ICBS2012 Catalyzes Robust Response from Global Chemical Biology Community.
Kinase Drug Discovery - What's Next in the Field?
Over the past 15 years protein kinases have become the pharmaceutical industry's most important class of drug target in the field of cancer. Some 20 drugs that target kinases have been approved for clinical use over the past decade, and hundreds more are undergoing clinical trials. However, the recent approval of the first protein kinase inhibitors for the treatment of inflammatory diseases, coupled with an enhanced understanding of the signaling networks that control the immune system, suggests that there...
Chemical biology - current and next challenges.
