Abstract
African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA aptamers as tools for the development of novel trypanocidal compounds. Here, we report the selection of a 2-NH2-modified RNA aptamer that binds to live trypanosomes with an affinity of 70 ± 15 nM. The aptamer adopts a stable G-quartet structure and has a half-life in human serum of ≥30 h. RNA binding is restricted to the flagellar attachment zone, located between the cell body and the flagellum of the parasite. We demonstrate that antigen-tagged preparations of the aptamer can bind to live trypanosomes and that they can be used to re-direct immunoglobulins to the parasite surface.
Keywords: G-quartet, African sleeping sickness, Trypanosoma brucei, African trypanosomes, RNA aptamer, SELEX
Combinatorial Chemistry & High Throughput Screening
Title: Serum-Stable RNA Aptamers to an Invariant Surface Domain of Live African Trypanosomes
Volume: 9 Issue: 7
Author(s): H. Ulrich Goringer, Martin Zacharias, Markus Engstler, Matthias Homann and Mihaela Lorger
Affiliation:
Keywords: G-quartet, African sleeping sickness, Trypanosoma brucei, African trypanosomes, RNA aptamer, SELEX
Abstract: African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA aptamers as tools for the development of novel trypanocidal compounds. Here, we report the selection of a 2-NH2-modified RNA aptamer that binds to live trypanosomes with an affinity of 70 ± 15 nM. The aptamer adopts a stable G-quartet structure and has a half-life in human serum of ≥30 h. RNA binding is restricted to the flagellar attachment zone, located between the cell body and the flagellum of the parasite. We demonstrate that antigen-tagged preparations of the aptamer can bind to live trypanosomes and that they can be used to re-direct immunoglobulins to the parasite surface.
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Cite this article as:
Ulrich Goringer H., Zacharias Martin, Engstler Markus, Homann Matthias and Lorger Mihaela, Serum-Stable RNA Aptamers to an Invariant Surface Domain of Live African Trypanosomes, Combinatorial Chemistry & High Throughput Screening 2006; 9 (7) . https://dx.doi.org/10.2174/138620706777935324
DOI https://dx.doi.org/10.2174/138620706777935324 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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