Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cervical cancer is the second most common cancer among women worldwide, with significantly higher rates in developing areas, especially in Africa, the Caribbean, and Latin America (Parkin, Bray, Ferlay, & Pisani, 2005). In contrast, incidence and mortality rates of cervical cancer in the United States have declined significantly among women of all ethnic and racial groups; it is not among the top 10 leading causes of new cancer cases in women (American Cancer Society [ACS], 2006b; Edwards et al.,2005).
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PMID:Cervical cancer: what should we tell women about screening? 1692 6

How caregivers relate to care recipients can affect how well care is provided and how much burden is experienced in providing it. We conceptualized the relationship of spousal caregivers via adult attachment theory and examined how attachment qualities of caregivers related to level of caregiving involvement and difficulties in caregiving. Gender differences in the associations were also explored. From participants in the ACS Quality of Life Survey for Caregivers, 400 spousal caregivers provided valid data for the study variables. Findings indicated that frequency of various types of care was a joint function of attachment orientation and gender. In contrast, the difficulty that caregivers experienced in providing care related directly to attachment, without moderation by gender. Our findings suggest that ineffective caregivers of cancer patients, who can be identified by their attachment orientation and/or gender, may benefit from educational programs to improve their caregiving skills and to encourage them to utilize resources from other family members or community.
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PMID:Frequency and difficulty in caregiving among spouses of individuals with cancer: effects of adult attachment and gender. 1709 51

A recent publication revealing that the cytotoxic marine natural product pateamine A targets eukaryotic initiation factor eIF4A continues a story with lessons for both chemists and biologists, that is, the significance of natural products, the importance of synthetic organic chemistry, the small molecule regulation of eukaryotic translation machinery, and possibly a new approach to cancer chemotherapy.
ACS Chem Biol 2006 Feb 17
PMID:Stopping trouble before it starts. 1716 34

Numerous host cellular cofactors are involved in the life cycle of retroviruses. Importantly, DNA repair machinery of infected cells is activated by retroviruses and retroviral vectors during the process of integration and host cell DNA repair proteins are employed to create a fully integrated provirus. The full delineation of these repair mechanisms that are triggered by retroviruses also has implications outside of the field of retrovirology. It will undoubtedly be of interest to developers of gene therapy and will also further facilitate our understanding of DNA repair and cancer. This review gives a brief summary of the accomplishments in the field of DNA repair and retroviral integration and the opportunities that this area of science provides with regards to the elucidation of repair mechanisms, in the context of retroviral infection.
ACS Chem Biol 2006 May 23
PMID:Following the path of the virus: the exploitation of host DNA repair mechanisms by retroviruses. 1716 76

The degree to which anticancer agents selectively target cancer cells is a key determinant in successful therapeutic outcomes. Inhibitors of the Hsp90 molecular chaperone represent an important new class of anticancer agents. We propose here a novel mechanism by which physiochemical properties of Hsp90 inhibitors can be optimized to increase selectivity towards cancer cells. The basis for this approach relies on differential intracellular pH gradients that have been shown to exist between normal and transformed cells. Five Hsp90 inhibitors containing basic or neutral properties were evaluated in antiproliferation assays using cells with variable lysosomal pH. Inhibitors with basic functionalities had reduced activity in cells with normal (low) lysosomal pH but showed significantly greater activity in cells with abnormally elevated lysosomal pH (similar to what has been recorded in many types of cancer cells). Conversely, such selectivity enhancement was not observed for neutral inhibitors. The mechanistic basis for the observed selectivity was demonstrated quantitatively by determining the concentration of inhibitors within relevant intracellular compartments. Collectively, these findings suggest that Hsp90 inhibitors with optimal basicity and physicochemical properties have enhanced selectivity toward cancer cells than their neutral counterparts. It is anticipated that these findings may be applicable to other classes of anticancer agents for improvement of differential selectivity.
ACS Chem Biol 2006 Jun 20
PMID:A new approach for enhancing differential selectivity of drugs to cancer cells. 1716 53

Soon after a sperm meets an egg, the single fertilized cell splits into two cells, then four, and then eight. Cell division is responsible for producing each of the trillions of cells present in every human body. During adulthood, division supplies replacements for cells lost to age, injury, and disease, but it can also form the basis for illnesses such as cancer. Despite the importance of mitosis in development and medicine, researchers have much to learn about the molecular mechanisms that regulate it. Cell biologist Rebecca Heald of the University of California, Berkeley, is striving to iron out these details. Heald's work concentrates on the mitotic spindle, a structure that is essential for correctly distributing copied chromosomes to daughter cells. Using techniques that blend biology and chemistry, she and her colleagues are identifying molecules and proteins that play major roles in directing this dynamic cell process.
ACS Chem Biol 2006 Oct 24
PMID:Divide and conquer: investigating the mechanisms behind mitosis. 1716 47

Mechanism-based probes are providing new tools to evaluate the enzymatic activities of protein families in complex mixtures and to assign protein function. The application of these chemical probes for the visualization of protein labeling in cells and proteomic analysis is still challenging. As a consequence, imaging and proteomic analysis often require different sets of chemical probes. Here we describe a mechanism-based probe, azido-E-64, that can be used for both imaging and proteomics. Azido-E-64 covalently modifies active Cathepsin (Cat) B in living cells, an abundant cysteine protease involved in microbial infections, apoptosis, and cancer. Furthermore, azido-E-64 contains an azide chemical handle that can be selectively derivatized with phosphine reagents via the Staudinger ligation, which enables the imaging and proteomic analysis of Cat B. We have utilized azido-E-64 to visualize active Cat B during infection of primary macrophages with Salmonella typhimurium , an facultative intracellular bacterial pathogen. These studies demonstrated that active Cat B is specifically excluded from Salmonella -containing vacuoles, which suggests that inhibition of protease activity within bacteria-containing vacuoles may contribute to bacterial virulence.
ACS Chem Biol 2006 Dec 20
PMID:Mechanism-based probe for the analysis of cathepsin cysteine proteases in living cells. 1718 36

The 4-hydroxy-2-pyrone moiety is commonly observed in polyketides generated via biosynthetic engineering of type II polyketide synthases. To explore the synthetic utility of these 2-pyrones, four engineered polyketides (mutactin, SEK4, SEK15, and SEK15b) were isolated from appropriate derivatives of Streptomyces coelicolor CH999. As a test case, we prepared nine novel pyranopyrones through condensation reactions with either citral, 1-cyclohexene-carboxaldehyde, or S-perillaldehyde. Synthetic tricyclic pyranopyrones with simple aromatic substituents are known to possess anticancer properties. We therefore investigated whether pyranopyrone derivatives of aromatic polyketides exhibited bioactivity in a panel of three cancer cell lines. Pyranopyrones generated from SEK4 had activity comparable to that of H10, a pyranopyrone with a 3-pyridyl substituent, whereas other analogues were less active. These results suggest that the diverse library of carbo- and heterocycles available through the genetic engineering of type II polyketide synthases can serve as useful building blocks to generate unique bioactive molecules.
ACS Chem Biol 2007 Feb 20
PMID:Synthesis and biological activity of novel pyranopyrones derived from engineered aromatic polyketides. 1725 96

This report highlights the advantages of low-affinity, multivalent interactions to recognize one cell type over another. Our goal was to devise a strategy to mediate selective killing of tumor cells, which are often distinguished from normal cells by their higher levels of particular cell surface receptors. To test whether multivalent interactions could lead to highly specific cell targeting, we used a chemically synthesized small-molecule ligand composed of two distinct motifs: (1) an Arg-Gly-Asp (RGD) peptidomimetic that binds tightly (Kd approximately 10(-9)M) to alphavbeta3 integrins and (2) the galactosyl-alpha(1-3)galactose (alpha-Gal epitope), which is recognized by human anti-alpha-galactosyl antibodies (anti-Gal). Importantly, anti-Gal binding requires a multivalent presentation of carbohydrate residues; anti-Gal antibodies interact weakly with the monovalent oligosaccharide (Kd approximately 10(-5)M) but bind tightly (Kd approximately 10(-11) M) to multivalent displays of alpha-Gal epitopes. Such a display is generated when the bifunctional conjugate decorates a cell possessing a high level of alphavbeta3 integrin; the resulting cell surface, which presents many alpha-Gal epitopes, can recruit anti-Gal, thereby triggering complement-mediated lysis. Only those cells with high levels of the integrin receptor are killed. In contrast, doxorubicin tethered to the RGD-based ligand affords indiscriminate cell death. These results highlight the advantages of exploiting the type of the multivalent recognition processes used by physiological systems to discriminate between cells. The selectivity of this strategy is superior to traditional, abiotic, high-affinity targeting methods. Our results have implications for the treatment of cancer and other diseases characterized by the presence of deleterious cells.
ACS Chem Biol 2007 Feb 20
PMID:Selective tumor cell targeting using low-affinity, multivalent interactions. 1729 Oct 50

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated in cancer. Three new crystal structures of PP2A show how it interacts with inhibitory toxins and with one of its regulatory subunits. The structures also explain how specific site mutations may lead to cancer and suggest a novel role for PP2A methylation in the formation of PP2A holoenzymes.
ACS Chem Biol 2007 Feb 20
PMID:The 3D structure of protein phosphatase 2A: new insights into a ubiquitous regulator of cell signaling. 1731 79


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