SYNTHETIC OLIGONUCLEOTIDES FOR TRYPANOSOME CHEMOTHERAPY

所有锥虫mRNA的5'末端最近已经被证明 具有共同的35个核苷酸的剪接前导序列（SL）。 SL是 被认为是通过小外显子衍生的 RNA（medRNA）约140个核苷酸，其次是其 与mRNA的初级转录物反式剪接。 的 所有锥虫mRNA中SL的存在提供了理想的 系统，以使短寡核苷酸的功效保持不变， 治疗剂。 合成寡核苷酸，由以下组成 二酯、乙基磷酸三酯或甲基膦酸酯，将被 合成了 这些将与SL序列互补，或 到medRNA的剪接供体位点，以直接抑制 蛋白质合成或mRNA成熟。 这些寡核苷酸 将测试它们抑制细胞中蛋白质合成的能力， 使用纯化的mRNA的游离系统，以及 布氏锥虫 特异性反义寡核苷酸将 提供有价值的化疗剂用于治疗 重要的人类疾病。

The 5' ends of all trypanosome mRNAs have recently been shown to have a common 35 nucleotide spliced leader (SL). The SL is believed to arise by transcription within a miniexonderived RNA (medRNA) of about 140 nucleotides, followed by its transsplicing with the primary transcripts of mRNAs. The presence of the SL in all trypanosomal mRNAs provides an ideal system to rest the efficacy of short oligonucleotides as therapeutic agents. Synthetic oligonucleotides, consisting of diesters, ethyl phosphotriesters or methylphosphonates, will be synthesized. These will be complementary to the SL sequence or to the splice donor site of the medRNA in order to directly inhibit protein synthesis or mRNA maturation. These oligonucleotides will be tested for their ability to inhibit protein synthesis in cell free systems using purified mRNA, and in cell cultures of Trypanosoma brucei. Specific, antisense oligonucleotides will provide valuable chemotherapeutic agents for the treatment of important human diseases.