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  • 1
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    Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-04-11
    Description: The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus-type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1-infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)-RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1-infected individuals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, G -- Clapham, P R -- Picard, L -- Offord, R E -- Rosenkilde, M M -- Schwartz, T W -- Buser, R -- Wells, T N -- Proudfoot, A E -- New York, N.Y. -- Science. 1997 Apr 11;276(5310):276-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Virology Group, Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9092481" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/metabolism ; Binding, Competitive ; Cats ; Cell Line ; Cells, Cultured ; Chemokine CCL4 ; Chemokine CCL5/metabolism/pharmacology ; Chemotaxis, Leukocyte ; HIV-1/*drug effects/physiology ; HeLa Cells ; Humans ; Macrophage Inflammatory Proteins/metabolism ; Macrophages/drug effects/*virology ; Receptors, CCR5 ; *Receptors, Chemokine ; Receptors, Cytokine/*antagonists & inhibitors/metabolism ; Receptors, HIV/*antagonists & inhibitors/metabolism ; T-Lymphocytes/drug effects/*virology ; Virus Replication/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-09-12
    Description: Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines. In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kledal, T N -- Rosenkilde, M M -- Coulin, F -- Simmons, G -- Johnsen, A H -- Alouani, S -- Power, C A -- Luttichau, H R -- Gerstoft, J -- Clapham, P R -- Clark-Lewis, I -- Wells, T N -- Schwartz, T W -- New York, N.Y. -- Science. 1997 Sep 12;277(5332):1656-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Molecular Pharmacology, Institute of Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9287217" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Cell Line ; Chemokine CCL5/antagonists & inhibitors ; Chemokines/*antagonists & inhibitors/chemistry/genetics/*metabolism/pharmacology ; Chemotaxis, Leukocyte ; HIV-1/physiology ; Herpesvirus 8, Human/*genetics ; Humans ; Molecular Sequence Data ; Monocytes/cytology ; Receptors, Cytokine/antagonists & inhibitors/*metabolism ; Receptors, HIV/antagonists & inhibitors/*metabolism ; Recombinant Proteins/pharmacology ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Structural biology: snapshot of a signalling complex (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-10-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwartz, Thue W -- Sakmar, Thomas P -- England -- Nature. 2011 Sep 28;477(7366):540-1. doi: 10.1038/477540a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. tws@sund.ku.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21956322" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; GTP-Binding Protein alpha Subunits, Gs/*chemistry/*metabolism ; Humans ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Somatostatin cell processes as pathways for paracrine secretion (1979)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1979-09-28
    Description: Somatostatin is produced by gastrointestinal endocrine cells that have long, nonluminal, cytoplasmic processes. Such processes terminate on other cell types, including gastrin-producing and hydrochloric acid-producing cells, whose functions are profoundly affected by somatostatin. The findings suggest that somatostatin cells control the functions of other cells through local release of the peptide by way of cytoplasmic processes. Also, certain other types of gastrointestinal endocrine cells have similar cytoplasmic prolongations, which may have analogous local (paracrine) regulatory functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larsson, L I -- Goltermann, N -- de Magistris, L -- Rehfeld, J F -- Schwartz, T W -- New York, N.Y. -- Science. 1979 Sep 28;205(4413):1393-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/382360" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gastric Juice/*secretion ; Gastrins/secretion ; Humans ; Immunoenzyme Techniques ; Pyloric Antrum/cytology/*metabolism ; Rats ; Somatostatin/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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