doi:10.1038/nindia.2008.226 Published online 17 June 2008
An Indian research team has designed a small protein molecule that inhibits the growth of the malaria bug inside the host's cells. The molecule blocks the activity of an enzyme used by the bug (Plasmodium falciparum) to devour haemoglobin and thrive on the red blood cells shortly after entering the human host1. This study raises the possibility of an antiparasitic drug of therapeutic interest.
To go around drug-resistant malaria-bugs, researchers are increasingly using drug targets known as cysteine proteases, a class of enzymes christened as falcipains. P. falciparum uses falcipains to invade and rupture the host's red blood cells. Research has shown that falcipains morph into active form by getting rid of specific bits known as propeptide regions that could otherwise block their activity.
This led the researchers to study the activity of propeptide regions against falcipains, specifically falcipain-2. A series of peptides from the identified regions of falcipain-2 were designed and their effects studied.
First, the active falcipain-2 was mixed with the designed peptides. Of the five designed peptides, peptide PP1 significantly inhibited the activity of falcipain-2.
"These peptides are not expected to affect the activity of human enzymes," says lead researcher Pawan Malhotra. "For the first time, we show the use of a synthetic peptide as an antimalarial effector," he says. This will be useful in designing synthetic peptides against multiple enzymes and explore their potential to control malaria parasite.
The authors of this work are from: International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India and Department of Zoology, Delhi University, Delhi, India.