The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of an N-terminal trimeric alpha-helical coiled coil domain, and three anti-parallel C-terminal helices which fold down the grooves of the coiled coil to form a six-helix bundle. Disruption of the six-helix bundle is considered to be a key component of an effective non-peptide fusion inhibitor. This structure forms as a more ..
Target
Depositor Specified Assays
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| AID | Name | Type | Comment |
|---|---|---|---|
| 1986 | uHTS fluorescence assay for the identification of Human Immunodeficiency Virus Fusion Inhibitors. | confirmatory | uHTS fluorescence assay for the identification of Human Immunodeficiency Virus Fusion Inhibitors. |
| 2279 | A Cell Based Assay for the Identification of Lead Compounds with Inhibitory Activity against HIV-1 Fusion (CCR5 Tropic HIV-1 Fusion Inhibition Assay) - Dose Response | confirmatory | Confirmatory assay |
| 2286 | A Cell Based Assay for the Identification of Lead Compounds with Inhibitory Activity against HIV-1 Fusion (CCR5 Tropic HIV-1 Fusion Inhibition Assay) - Cytotoxicity Counter Screen - Dose Response | confirmatory | Confirmatory assay |
| 2644 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay | confirmatory | Secondary Assay |
| 2649 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen | confirmatory | Cytotox Assay |
| 2788 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (2) | confirmatory | |
| 2812 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (2) | confirmatory | |
| 434967 | SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion. | confirmatory | |
| 435029 | SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion, cell-cell fusion assay | confirmatory | |
| 435031 | SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion, cytoxicity assay | confirmatory | |
| 493095 | SAR analysis of compounds that inhibit Human Immunodeficiency Virus Fusion -Set 2 | confirmatory | |
| 504341 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (1) | confirmatory | |
| 504352 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (3) | confirmatory | |
| 504363 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Dose Response | confirmatory | |
| 504367 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response | confirmatory | |
| 504388 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen | confirmatory | |
| 504393 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen | confirmatory | |
| 504394 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen | confirmatory | |
| 504395 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (3) | confirmatory | |
| 504484 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response | confirmatory | |
| 504503 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response | confirmatory | |
| 504530 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Response | confirmatory | |
| 504551 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (2) | confirmatory | |
| 504553 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Assay (4) | confirmatory | |
| 504560 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (2) | confirmatory | |
| 504561 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Dose Response (2) | confirmatory | |
| 504563 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (2) | confirmatory | |
| 504570 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Dose Response (2) | confirmatory | |
| 504571 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Response (2) | confirmatory | |
| 504573 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen (2) | confirmatory | |
| 504574 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 Fusion Inhibition Assay) - Secondary Cytotoxicity Screen (2) | confirmatory | |
| 504575 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CXCR4-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (2) | confirmatory | |
| 504576 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (CCR5-Tropic HIV-1 MAGI Antiviral Assay) - Secondary Cytotoxicity Screen (4) | confirmatory | |
| 504625 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CXCR4-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (3) | confirmatory | |
| 504626 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against CCR5-tropic HIV-1 (HIV-1 PBMC Assay) - Dose Response (3) | confirmatory | |
| 504630 | A Cell Based Assay for the Characterization of Lead Compounds with Antiviral Activity against HIV-1 (HIV-1 PBMC Assay) - Cytotoxicity Counter Screen - Dose Response (3) | confirmatory |
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Production Centers Network (MLPCN)
Grant Number: 1R21NS059403-01
Assay Provider: Dr. Miriam Gochin, Touro University-California, Vallejo, CA
The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of an N-terminal trimeric alpha-helical coiled coil domain, and three anti-parallel C-terminal helices which fold down the grooves of the coiled coil to form a six-helix bundle. Disruption of the six-helix bundle is considered to be a key component of an effective non-peptide fusion inhibitor. This structure forms as a result of a conformational change in gp41, triggered by gp120 and co-receptor binding to host cell receptors. Prevention of six-helix bundle formation has been recognized as an important mechanism for viral fusion inhibition
A metallopeptide-based fluorescence assay has been developed to detect HIV-1 fusion inhibitors, by the screening of small molecules that bind to the hydrophobic pocket of gp41. The assay involves two peptides representing the inner N-terminal-heptad-repeat (HR1) coiled coil and the outer C-terminal-heptad-repeat (HR2) helical domains of the gp41 six-helix bundle which forms prior to fusion. The HR1 peptide is modified with a metal-ligated dye complex, which maintains structural integrity and permits association with a fluorescein-labeled HR2 peptide concomitant with fluorescence quenching. Compounds able to disrupt six-helix bundle formation can act as fusion inhibitors, and can be detected in the assay from an increase in the fluorescence that is correlated with compound's efficacy.
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Production Centers Network (MLPCN)
Grant Number: 1R21NS059403-01
Assay Provider: Dr. Miriam Gochin, Touro University-California, Vallejo, CA
The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of an N-terminal trimeric alpha-helical coiled coil domain, and three anti-parallel C-terminal helices which fold down the grooves of the coiled coil to form a six-helix bundle. Disruption of the six-helix bundle is considered to be a key component of an effective non-peptide fusion inhibitor. This structure forms as a result of a conformational change in gp41, triggered by gp120 and co-receptor binding to host cell receptors. Prevention of six-helix bundle formation has been recognized as an important mechanism for viral fusion inhibition
A metallopeptide-based fluorescence assay has been developed to detect HIV-1 fusion inhibitors, by the screening of small molecules that bind to the hydrophobic pocket of gp41. The assay involves two peptides representing the inner N-terminal-heptad-repeat (HR1) coiled coil and the outer C-terminal-heptad-repeat (HR2) helical domains of the gp41 six-helix bundle which forms prior to fusion. The HR1 peptide is modified with a metal-ligated dye complex, which maintains structural integrity and permits association with a fluorescein-labeled HR2 peptide concomitant with fluorescence quenching. Compounds able to disrupt six-helix bundle formation can act as fusion inhibitors, and can be detected in the assay from an increase in the fluorescence that is correlated with compound's efficacy.
Protocol
Please see pertinent AIDs: 1986, 2279, 2286, 2644, 2649, 2788, 2812, 434967, 435029, 435031, 493095, 504341, 504352, 504363, 504367, 504388, 504393, 504394, 504395, 504484, 504503, 504530, 504551, 504553, 504560, 504561, 504563, 504570, 504571, 504573, 504574, 504575, 504576, 504625, 504626, 504630
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Additional Information
Grant Number: 1R21NS059403-01
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