G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum

Telomeres are DNA and protein structures located at the ends of eukaryotic chromosomes. These structures maintain chromosomal stability by impeding chromosomal ends from being recognized and processed as fragmented DNA. They also support the complete replication of the genome by providing mechanisms...

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Autores:
Calvo, Eliana
Wasserman, M.
Tipo de recurso:
Article of journal
Fecha de publicación:
2020
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/3667
Acceso en línea:
http://hdl.handle.net/20.500.12495/3667
https://doi.org/10.1016/j.molbiopara.2016.05.009
https://repositorio.unbosque.edu.co
Palabra clave:
Malaria
Plasmodium falciparum
Telomere
Telomerase
G-quadruplex
Telomestatin
TMPyP4
Rights
openAccess
License
Acceso abierto
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repository_id_str
dc.title.spa.fl_str_mv G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
dc.title.translated.spa.fl_str_mv G-quadruplex ligands: potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
title G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
spellingShingle G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
Malaria
Plasmodium falciparum
Telomere
Telomerase
G-quadruplex
Telomestatin
TMPyP4
title_short G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
title_full G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
title_fullStr G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
title_full_unstemmed G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
title_sort G-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparum
dc.creator.fl_str_mv Calvo, Eliana
Wasserman, M.
dc.contributor.author.none.fl_str_mv Calvo, Eliana
Wasserman, M.
dc.contributor.orcid.none.fl_str_mv Calvo, Eliana [0000-0002-9135-0748]
dc.subject.keywords.spa.fl_str_mv Malaria
Plasmodium falciparum
Telomere
Telomerase
G-quadruplex
Telomestatin
TMPyP4
topic Malaria
Plasmodium falciparum
Telomere
Telomerase
G-quadruplex
Telomestatin
TMPyP4
description Telomeres are DNA and protein structures located at the ends of eukaryotic chromosomes. These structures maintain chromosomal stability by impeding chromosomal ends from being recognized and processed as fragmented DNA. They also support the complete replication of the genome by providing mechanisms that solve the end-replication problem. Telomeric DNA is formed of short, repeating, guanine-rich sequences. The G-rich sequence extends towards the 3′ end, forming a protruding single-stranded end that can acquire a conformation known as G-quadruplex. The ligands stabilizing this structure are potent inhibitors of telomerase activity, a catalytic activity necessary to compensate for the loss of telomeric DNA that occurs in each round of replication. In the absence of telomerase, telomeres shorten after a given number of cell divisions, after which the cell enters a senescence state and finally dies. In the presence of telomerase activity, telomeres are preserved, and cells reach a state of indefinite replication or immortalization. This study analyzed the effect of two ligands of the G-quadruplex (TMPyP4 and Telomestatin) on the telomerase activity and cell proliferation of Plasmodium falciparum, given that this parasite has a high proliferation rate and an almost indefinite replication capacity. The effect of the ligands on telomerase activity was evaluated using the TRAP (Telomere Repeat Amplification Protocol) activity assay, which was performed in the presence of increasing concentrations of each ligand. In this study, TMPyP4 showed the highest inhibitory effect, reaching 50% inhibition at a 5 μM concentration. Regarding proliferation, both ligands drastically affected parasite growth, but Telomestatin had a stronger effect. After three days of treatment, parasite growth decreased by 90%. Thus, it is possible that this compound interferes with other vital pathways for the parasite beyond the elongation of telomeric DNA by telomerase.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-08-04T20:13:13Z
dc.date.available.none.fl_str_mv 2020-08-04T20:13:13Z
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dc.type.local.none.fl_str_mv Artículo de revista
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dc.identifier.issn.none.fl_str_mv 1872-9428
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/3667
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1016/j.molbiopara.2016.05.009
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
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identifier_str_mv 1872-9428
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
url http://hdl.handle.net/20.500.12495/3667
https://doi.org/10.1016/j.molbiopara.2016.05.009
https://repositorio.unbosque.edu.co
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Molecular and Biochemical Parasitology, 1872-9428, Vol. 207, Nro. 1,2016, p. 33-38
dc.relation.uri.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0166685116300603?via%3Dihub
dc.rights.local.spa.fl_str_mv Acceso abierto
dc.rights.accessrights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
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Acceso abierto
dc.rights.creativecommons.none.fl_str_mv 2016-03
rights_invalid_str_mv Acceso abierto
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2016-03
eu_rights_str_mv openAccess
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dc.publisher.spa.fl_str_mv Elsevier
dc.publisher.journal.spa.fl_str_mv Molecular and Biochemical Parasitology
institution Universidad El Bosque
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spelling Calvo, ElianaWasserman, M.Calvo, Eliana [0000-0002-9135-0748]2020-08-04T20:13:13Z2020-08-04T20:13:13Z1872-9428http://hdl.handle.net/20.500.12495/3667https://doi.org/10.1016/j.molbiopara.2016.05.009instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquehttps://repositorio.unbosque.edu.coapplication/pdfengElsevierMolecular and Biochemical ParasitologyMolecular and Biochemical Parasitology, 1872-9428, Vol. 207, Nro. 1,2016, p. 33-38https://www.sciencedirect.com/science/article/pii/S0166685116300603?via%3DihubG-quadruplex ligands:potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparumG-quadruplex ligands: potent inhibitors of telomerase activity and cell proliferation in plasmodium falciparumArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85MalariaPlasmodium falciparumTelomereTelomeraseG-quadruplexTelomestatinTMPyP4Telomeres are DNA and protein structures located at the ends of eukaryotic chromosomes. These structures maintain chromosomal stability by impeding chromosomal ends from being recognized and processed as fragmented DNA. They also support the complete replication of the genome by providing mechanisms that solve the end-replication problem. Telomeric DNA is formed of short, repeating, guanine-rich sequences. The G-rich sequence extends towards the 3′ end, forming a protruding single-stranded end that can acquire a conformation known as G-quadruplex. The ligands stabilizing this structure are potent inhibitors of telomerase activity, a catalytic activity necessary to compensate for the loss of telomeric DNA that occurs in each round of replication. In the absence of telomerase, telomeres shorten after a given number of cell divisions, after which the cell enters a senescence state and finally dies. In the presence of telomerase activity, telomeres are preserved, and cells reach a state of indefinite replication or immortalization. This study analyzed the effect of two ligands of the G-quadruplex (TMPyP4 and Telomestatin) on the telomerase activity and cell proliferation of Plasmodium falciparum, given that this parasite has a high proliferation rate and an almost indefinite replication capacity. The effect of the ligands on telomerase activity was evaluated using the TRAP (Telomere Repeat Amplification Protocol) activity assay, which was performed in the presence of increasing concentrations of each ligand. In this study, TMPyP4 showed the highest inhibitory effect, reaching 50% inhibition at a 5 μM concentration. Regarding proliferation, both ligands drastically affected parasite growth, but Telomestatin had a stronger effect. After three days of treatment, parasite growth decreased by 90%. Thus, it is possible that this compound interferes with other vital pathways for the parasite beyond the elongation of telomeric DNA by telomerase.Acceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2016-03LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/00be0066-c30f-4b27-a43b-cc2127fa3dc2/download8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINALCalvo, E.P..pdfCalvo, E.P..pdfapplication/pdf964203https://repositorio.unbosque.edu.co/bitstreams/23366959-6a16-43f5-b929-7acb6460ecd4/downloadb9155cf57d5172d167e1d167bd11bf96MD51THUMBNAILCalvo, E.P.pdf.jpgCalvo, E.P.pdf.jpgimage/jpeg5775https://repositorio.unbosque.edu.co/bitstreams/4755bec9-a118-4469-b910-dcf13143c51e/download7210a811635d1799e7c05fee5d259be7MD53Calvo, E.P..pdf.jpgCalvo, E.P..pdf.jpgIM Thumbnailimage/jpeg9812https://repositorio.unbosque.edu.co/bitstreams/040521af-4914-4f3e-b1d6-6620ef8f23ea/downloadbc7d350ffe15739d10002e2374de4025MD54TEXTCalvo, E.P..pdf.txtCalvo, E.P..pdf.txtExtracted texttext/plain100319https://repositorio.unbosque.edu.co/bitstreams/a66cf64f-f4bb-4f49-a65e-16d5ea8af6bb/download62147ac6da84a5b1bab80eef802472c7MD5520.500.12495/3667oai:repositorio.unbosque.edu.co:20.500.12495/36672024-02-07 13:05:13.229restrictedhttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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