Display Settings:

Format

Send to:

Choose Destination
Malar J. 2012 Aug 1;11:256. doi: 10.1186/1475-2875-11-256.

Anti-plasmodial action of de novo-designed, cationic, lysine-branched, amphipathic, helical peptides.

Author information

  • 1Malaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Abstract

BACKGROUND:

A lack of vaccine and rampant drug resistance demands new anti-malarials.

METHODS:

In vitro blood stage anti-plasmodial properties of several de novo-designed, chemically synthesized, cationic, amphipathic, helical, antibiotic peptides were examined against Plasmodium falciparum using SYBR Green assay. Mechanistic details of anti-plasmodial action were examined by optical/fluorescence microscopy and FACS analysis.

RESULTS:

Unlike the monomeric decapeptides {(Ac-GXRKXHKXWA-NH2) (X = F,ΔF) (Fm, ΔFm IC50 >100 μM)}, the lysine-branched,dimeric versions showed far greater potency {IC50 (μM) Fd 1.5 , ΔFd 1.39}. The more helical and proteolytically stable ΔFd was studied for mechanistic details. ΔFq, a K-K2 dendrimer of ΔFm and (ΔFm)2 a linear dimer of ΔFm showed IC50 (μM) of 0.25 and 2.4 respectively. The healthy/infected red cell selectivity indices were >35 (ΔFd), >20 (ΔFm)2 and 10 (ΔFq). FITC-ΔFd showed rapid and selective accumulation in parasitized red cells. Overlaying DAPI and FITC florescence suggested that ΔFd binds DNA. Trophozoites and schizonts incubated with ΔFd (2.5 μM) egressed anomalously and Band-3 immunostaining revealed them not to be associated with RBC membrane. Prematurely egressed merozoites from peptide-treated cultures were found to be invasion incompetent.

CONCLUSION:

Good selectivity (>35), good resistance index (1.1) and low cytotoxicity indicate the promise of ΔFd against malaria.

PMID:
22853877
[PubMed - indexed for MEDLINE]
PMCID:
PMC3502156
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk