Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides
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...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2012
|
Subjects: | |
Online Access: | https://doi.org/10.1186/1475-2875-11-256 https://doaj.org/article/0ee38c1613874be8b49f41205c2aae14 |
id |
ftdoajarticles:oai:doaj.org/article:0ee38c1613874be8b49f41205c2aae14 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:0ee38c1613874be8b49f41205c2aae14 2023-05-15T15:11:14+02:00 Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides Kaushik Naveen K Sharma Jyotsna Sahal Dinkar 2012-08-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-256 https://doaj.org/article/0ee38c1613874be8b49f41205c2aae14 EN eng BMC http://www.malariajournal.com/content/11/1/256 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-256 1475-2875 https://doaj.org/article/0ee38c1613874be8b49f41205c2aae14 Malaria Journal, Vol 11, Iss 1, p 256 (2012) Anomalous egress Anti-plasmodial peptides De novo peptide design Kinetics of peptide uptake Peptide binding to DNA Plasmodium falciparum Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-256 2022-12-30T22:17:05Z 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-NH 2 ) (X = F,ΔF) (Fm , ΔFm IC 50 >100 μM)}, the lysine-branched,dimeric versions showed far greater potency {IC 50 (μM) Fd 1.5 , ΔFd 1.39}. The more helical and proteolytically stable ΔFd was studied for mechanistic details. ΔFq, a K-K 2 dendrimer of ΔFm and (ΔFm) 2 a linear dimer of ΔFm showed IC 50 (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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 256 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Anomalous egress Anti-plasmodial peptides De novo peptide design Kinetics of peptide uptake Peptide binding to DNA Plasmodium falciparum Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Anomalous egress Anti-plasmodial peptides De novo peptide design Kinetics of peptide uptake Peptide binding to DNA Plasmodium falciparum Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Kaushik Naveen K Sharma Jyotsna Sahal Dinkar Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
topic_facet |
Anomalous egress Anti-plasmodial peptides De novo peptide design Kinetics of peptide uptake Peptide binding to DNA Plasmodium falciparum Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
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-NH 2 ) (X = F,ΔF) (Fm , ΔFm IC 50 >100 μM)}, the lysine-branched,dimeric versions showed far greater potency {IC 50 (μM) Fd 1.5 , ΔFd 1.39}. The more helical and proteolytically stable ΔFd was studied for mechanistic details. ΔFq, a K-K 2 dendrimer of ΔFm and (ΔFm) 2 a linear dimer of ΔFm showed IC 50 (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. |
format |
Article in Journal/Newspaper |
author |
Kaushik Naveen K Sharma Jyotsna Sahal Dinkar |
author_facet |
Kaushik Naveen K Sharma Jyotsna Sahal Dinkar |
author_sort |
Kaushik Naveen K |
title |
Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
title_short |
Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
title_full |
Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
title_fullStr |
Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
title_full_unstemmed |
Anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
title_sort |
anti-plasmodial action of de novo -designed, cationic, lysine-branched, amphipathic, helical peptides |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-256 https://doaj.org/article/0ee38c1613874be8b49f41205c2aae14 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 256 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/256 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-256 1475-2875 https://doaj.org/article/0ee38c1613874be8b49f41205c2aae14 |
op_doi |
https://doi.org/10.1186/1475-2875-11-256 |
container_title |
Malaria Journal |
container_volume |
11 |
container_issue |
1 |
container_start_page |
256 |
_version_ |
1766342130656083968 |