Allosteric Site Inhibitor Disrupting Auto-Processing of Malarial Cysteine Proteases.

ABSTRACT: Falcipains are major haemoglobinases of Plasmodium falciparum required for parasite growth and development. They consist of pro- and mature domains that interact via 'hot-spot' interactions and maintain the structural integrity of enzyme in zymogen state. Upon sensing the acidic environment, these interactions dissociate and active enzyme is released. For inhibiting falcipains, several active site inhibitors exist, however, compounds that target via allosteric mechanism remains uncharacterized. Therefore, we designed and synthesized six azapeptide compounds, among which, NA-01 & NA-03 arrested parasite growth by specifically blocking the auto-processing of falcipains. Inhibitors showed high affinity for enzymes in presence of the prodomain without affecting the secondary structure. Binding

SUBMITTER: Pant A 

PROVIDER: S-EPMC6212536 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature