مورد إلكتروني
Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck.
| العنوان: | Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck. |
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| المؤلفون: | Olszewski, Allison |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America; vol 101, iss 39, 14079-14084; 0027-8424 |
| بيانات النشر: | eScholarship, University of California 2004-09-01 |
| تفاصيل مُضافة: | Olszewski, Allison Sato, Ken Aron, Zachary D Cohen, Frederick Harris, Aleishia McDougall, Brenda R Robinson, W Edward Overman, Larry E Weiss, Gregory A |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | With current anti-HIV treatments targeting only 4 of the 15 HIV proteins, many potential viral vulnerabilities remain unexploited. We report small-molecule inhibitors of the HIV-1 protein Nef. In addition to expanding the anti-HIV arsenal, small-molecule inhibitors against untargeted HIV proteins could be used to dissect key events in the HIV lifecycle. Numerous incompletely characterized interactions between Nef and cellular ligands, for example, present a challenge to understanding molecular events during HIV progression to AIDS. Assays with phage-displayed Nef from HIV(NL4-3) were used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck). The guanidines, synthetic analogs of batzellidine and crambescidin natural products, inhibit the Nef-ligand interactions with IC(50) values in the low micromolar range. In addition, sensitive in vivo assays for Nef inhibition are reported. Although compounds that are effective in vitro proved to be too cytotoxic for cellular assays, the reported Nef inhibitors provide proof-of-concept for disrupting a new HIV target and offer useful leads for drug development. |
| مصطلحات الفهرس: | T-Lymphocytes, Cell Line, Humans, HIV-1, Cell Transformation, Viral, Guanidine, Alkaloids, Actins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Peptide Library, Gene Products, nef, Recombinant Proteins, Anti-HIV Agents, Enzyme-Linked Immunosorbent Assay, Polymerase Chain Reaction, Inhibitory Concentration 50, Virus Replication, Molecular Structure, Structure-Activity Relationship, Dose-Response Relationship, Drug, Tumor Suppressor Protein p53, nef Gene Products, Human Immunodeficiency Virus, CD4 Antigens, HIV/AIDS, Infectious Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, article |
| URL: | |
| الإتاحة: | Open access content. Open access content CC-BY |
| ملاحظة: | application/pdf Proceedings of the National Academy of Sciences of the United States of America vol 101, iss 39, 14079-14084 0027-8424 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt6r9405g7 qt6r9405g7 https://escholarship.org/uc/item/6r9405g7 https://escholarship.org/ 1367444580 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1367444580 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |