Evaluation of 'Credit Card' Libraries for Inhibition of HIV-1 gp41 Fusogenic Core Formation
| Autor: | Laura A. McAllister, Jack P. Kennedy, Noboru Yamamoto, Xuxia Yan, Shibo Jiang, Jason A. Moss, Kim D. Janda, Grant E. Boldt, Yang Xu, Hong Lu |
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| Rok vydání: | 2006 |
| Předmět: |
Chemistry
Cell Membrane Molecular Sequence Data Drug Evaluation Preclinical General Chemistry Computational biology Viral antigen Plasma protein binding Gp41 Membrane Fusion Small molecule HIV Envelope Protein gp41 Article Cell Line Credit card Biochemistry HIV Fusion Inhibitors Core formation Animals Humans Spectrophotometry Ultraviolet Amino Acid Sequence Peptide sequence Hiv 1 gp41 Protein Binding |
| Zdroj: | Journal of Combinatorial Chemistry. 8:531-539 |
| ISSN: | 1520-4774 1520-4766 |
| Popis: | Protein-protein interactions are of critical importance in biological systems and small molecule modulators of such protein recognition and intervention processes are of particular interests. To investigate this area of research, we have synthesized small molecule libraries that can disrupt a number of biologically relevant protein-protein interactions. These library members are designed upon planar motifs, appended with a variety of chemical functions, which we have termed as “credit-card” structures. From two of our “credit-card” libraries, a series of molecules were uncovered which act as inhibitors against the HIV-1 gp41 fusogenic 6-helix bundle core formation, viral antigen p24 formation and cell-cell fusion at low micromolar concentrations. From the high-throughput screening assays we utilized, a selective index (SI) value of 4.2 was uncovered for compound 2261, which bodes well for future structure activity investigations and the design of more potent gp41 inhibitors. |
| Databáze: | OpenAIRE |
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