Summary of project PR002709
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002709. The data can be accessed directly via it's Project DOI: 10.21228/M8GV8W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002709 |
| Project DOI: | doi: 10.21228/M8GV8W |
| Project Title: | Deconvolution of the on-target activity of plasmepsin V peptidomimetics in P. falciparum parasites |
| Project Summary: | Plasmepsin V (PMV), an essential aspartyl protease, plays a critical role during the asexual blood stage of infection of Plasmodium by enabling the export of parasite proteins into the host red blood cell. This export is vital for parasite survival and pathogenesis, making PMV an attractive target for antimalarial drug development. Peptidomimetic inhibitors designed to mimic the natural substrate of PMV have demonstrated potent parasite-killing activity by blocking protein export. While these compounds have been instrumental in validating PMV as a bona fide antimalarial target, inconsistencies between their biochemical potency and cellular activity have raised questions regarding their precise mechanism of action. In this study, we employed chemoproteomic approaches, including solvent induced protein precipitation and intact-cell thermal profiling, to demonstrate PMV target engagement by the peptidomimetics. To further support these findings, we generated parasite lines exhibiting reduced sensitivity to peptidomimetics. Through whole-genome sequencing of these parasite lines, a single nucleotide variant within the pmv gene was revealed. This mutation was later validated using reverse genetics, confirming its role in mediating resistance. Together, these data provide strong evidence that the peptidomimetics exert their antimalarial activity by directly targeting PMV. These findings further support the potential of PMV as a validated and promising target for future antimalarial drug development. |
| Institute: | Monash University |
| Last Name: | Siddiqui |
| First Name: | Ghizal |
| Address: | 381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia |
| Email: | ghizal.siddiqui@monash.edu |
| Phone: | 99039282 |
Summary of all studies in project PR002709
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004290 | Metabolomics characterisation of Plasmodium falciparum response to plasmepsin V peptidomimetic inhibitors - 5 hour treatment | Plasmodium falciparum | Monash University | MS | 2025-11-03 | 1 | 24 | Uploaded data (2.7G)* |
| ST004291 | Metabolomics analysis of Plasmodium falciparum asexual-stage parasites treated with plasmepsin V peptidomimetics - 16 hour treatment | Plasmodium falciparum | Monash University | MS | 2025-11-03 | 1 | 13 | Uploaded data (1.4G)* |
