Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting
Abstract Background Early detection is crucial for the effective treatment of malaria, particularly in those cases infected with Plasmodium falciparum. There is a need for diagnostic devices with the capacity to distinguish P. falciparum from other strains of malaria. Here, aptamers generated agains...
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ftdoajarticles:oai:doaj.org/article:e5d1265b473b4c0c9b04527ca66a2577 2023-05-15T15:14:40+02:00 Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting Kelly-Anne Frith Ronen Fogel J. P. Dean Goldring Robert G. E. Krause Makobetsa Khati Heinrich Hoppe Mary E. Cromhout Meesbah Jiwaji Janice L. Limson 2018-05-01T00:00:00Z https://doi.org/10.1186/s12936-018-2336-z https://doaj.org/article/e5d1265b473b4c0c9b04527ca66a2577 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2336-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2336-z 1475-2875 https://doaj.org/article/e5d1265b473b4c0c9b04527ca66a2577 Malaria Journal, Vol 17, Iss 1, Pp 1-16 (2018) Aptamer Oligonucleotide Lactate dehydrogenase Malaria Biorecognition Detection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2336-z 2022-12-31T12:13:06Z Abstract Background Early detection is crucial for the effective treatment of malaria, particularly in those cases infected with Plasmodium falciparum. There is a need for diagnostic devices with the capacity to distinguish P. falciparum from other strains of malaria. Here, aptamers generated against targeted species-specific epitopes of P. falciparum lactate dehydrogenase (rPfLDH) are described. Results Two classes of aptamers bearing high binding affinity and specificity for recombinant P. falciparum lactate dehydrogenase (rPfLDH) and P. falciparum-specific lactate dehydrogenase epitopic oligopeptide (LDHp) were separately generated. Structurally-relevant moieties with particular consensus sequences (GGTAG and GGCG) were found in aptamers reported here and previously published, confirming their importance in recognition of the target, while novel moieties particular to this work (ATTAT and poly-A stretches) were identified. Aptamers with diagnostically-supportive functions were synthesized, prime examples of which are the aptamers designated as LDHp 1, LDHp 11 and rLDH 4 and rLDH 15 in work presented herein. Of the sampled aptamers raised against the recombinant protein, rLDH 4 showed the highest binding to the target rPfLDH in the ELONA assay, with both rLDH 4 and rLDH 15 indicating an ability to discriminate between rPfLDH and rPvLDH. LDHp 11 was generated against a peptide selected as a unique P. falciparum LDH peptide. The aptamer, LDHp 11, like antibodies against the same peptide, only detected rPfLDH and discriminated between rPfLDH and rPvLDH. This was supported by affinity binding experiments where only aptamers generated against a unique species-specific epitope showed an ability to preferentially bind to rPfLDH relative to rPvLDH rather than those generated against the whole recombinant protein. In addition, rLDH 4 and LDHp 11 demonstrated in situ binding to P. falciparum cells during confocal microscopy. Conclusions The utilization and application of LDHp 11, an aptamer generated against a unique ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 17 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Aptamer Oligonucleotide Lactate dehydrogenase Malaria Biorecognition Detection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Aptamer Oligonucleotide Lactate dehydrogenase Malaria Biorecognition Detection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Kelly-Anne Frith Ronen Fogel J. P. Dean Goldring Robert G. E. Krause Makobetsa Khati Heinrich Hoppe Mary E. Cromhout Meesbah Jiwaji Janice L. Limson Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
topic_facet |
Aptamer Oligonucleotide Lactate dehydrogenase Malaria Biorecognition Detection Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Early detection is crucial for the effective treatment of malaria, particularly in those cases infected with Plasmodium falciparum. There is a need for diagnostic devices with the capacity to distinguish P. falciparum from other strains of malaria. Here, aptamers generated against targeted species-specific epitopes of P. falciparum lactate dehydrogenase (rPfLDH) are described. Results Two classes of aptamers bearing high binding affinity and specificity for recombinant P. falciparum lactate dehydrogenase (rPfLDH) and P. falciparum-specific lactate dehydrogenase epitopic oligopeptide (LDHp) were separately generated. Structurally-relevant moieties with particular consensus sequences (GGTAG and GGCG) were found in aptamers reported here and previously published, confirming their importance in recognition of the target, while novel moieties particular to this work (ATTAT and poly-A stretches) were identified. Aptamers with diagnostically-supportive functions were synthesized, prime examples of which are the aptamers designated as LDHp 1, LDHp 11 and rLDH 4 and rLDH 15 in work presented herein. Of the sampled aptamers raised against the recombinant protein, rLDH 4 showed the highest binding to the target rPfLDH in the ELONA assay, with both rLDH 4 and rLDH 15 indicating an ability to discriminate between rPfLDH and rPvLDH. LDHp 11 was generated against a peptide selected as a unique P. falciparum LDH peptide. The aptamer, LDHp 11, like antibodies against the same peptide, only detected rPfLDH and discriminated between rPfLDH and rPvLDH. This was supported by affinity binding experiments where only aptamers generated against a unique species-specific epitope showed an ability to preferentially bind to rPfLDH relative to rPvLDH rather than those generated against the whole recombinant protein. In addition, rLDH 4 and LDHp 11 demonstrated in situ binding to P. falciparum cells during confocal microscopy. Conclusions The utilization and application of LDHp 11, an aptamer generated against a unique ... |
format |
Article in Journal/Newspaper |
author |
Kelly-Anne Frith Ronen Fogel J. P. Dean Goldring Robert G. E. Krause Makobetsa Khati Heinrich Hoppe Mary E. Cromhout Meesbah Jiwaji Janice L. Limson |
author_facet |
Kelly-Anne Frith Ronen Fogel J. P. Dean Goldring Robert G. E. Krause Makobetsa Khati Heinrich Hoppe Mary E. Cromhout Meesbah Jiwaji Janice L. Limson |
author_sort |
Kelly-Anne Frith |
title |
Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
title_short |
Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
title_full |
Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
title_fullStr |
Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
title_full_unstemmed |
Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting |
title_sort |
towards development of aptamers that specifically bind to lactate dehydrogenase of plasmodium falciparum through epitopic targeting |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2336-z https://doaj.org/article/e5d1265b473b4c0c9b04527ca66a2577 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-16 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2336-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2336-z 1475-2875 https://doaj.org/article/e5d1265b473b4c0c9b04527ca66a2577 |
op_doi |
https://doi.org/10.1186/s12936-018-2336-z |
container_title |
Malaria Journal |
container_volume |
17 |
container_issue |
1 |
_version_ |
1766345102201978880 |