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Specific inhibition of formation of transcription complexes by a calicheamicin oligosaccharide: a paradigm for the development of transcriptional antagonists.

作者信息

Ho S N, Boyer S H, Schreiber S L, Danishefsky S J, Crabtree G R

机构信息

Department of Pathology, Stanford University School of Medicine, CA 94305.

出版信息

Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9203-7. doi: 10.1073/pnas.91.20.9203.

DOI:10.1073/pnas.91.20.9203
PMID:7937742
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC44780/
Abstract

Sequence-specific DNA ligands that antagonize DNA-protein interactions represent a potentially powerful means of modulating gene expression. Calicheamicin gamma 1I, a member of the DNA-cleaving enediyne class of anticancer antibiotics, binds to specific DNA sequences through an aryltetrasaccharide domain. To take advantage of this unique sequence-specific recognition capability, the methyl glycoside of the aryltetrasaccharide of calicheamicin gamma 1I (CLM-MG) was used to investigate the ability of glycoconjugate DNA ligands to inhibit DNA-protein interactions. CLM-MG inhibits the formation of DNA-protein complexes at micromolar concentrations in a sequence-specific manner and rapidly dissociates preformed complexes. CLM-MG also inhibits transcription in vivo with similar sequence specificity. These results suggest a strategy for the development of a class of novel biological probes and therapeutic agents.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/38c7038678c5/pnas01142-0019-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/3ac033b4a798/pnas01142-0018-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/a0129c6b98d4/pnas01142-0019-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/38c7038678c5/pnas01142-0019-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/3ac033b4a798/pnas01142-0018-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/a0129c6b98d4/pnas01142-0019-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40c/44780/38c7038678c5/pnas01142-0019-b.jpg

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1
Specific inhibition of formation of transcription complexes by a calicheamicin oligosaccharide: a paradigm for the development of transcriptional antagonists.
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2
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本文引用的文献

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A strategy for the solid-phase synthesis of oligosaccharides.一种寡糖固相合成的策略。
Science. 1993 May 28;260(5112):1307-9. doi: 10.1126/science.8493573.
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Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex.活化T细胞淋巴特异性核因子（NF-AT）复合体的核成分与胞质成分的特性分析。
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HMG I(Y) interferes with the DNA binding of NF-AT factors and the induction of the interleukin 4 promoter in T cells.HMG I(Y)干扰T细胞中NF-AT因子与DNA的结合以及白细胞介素4启动子的诱导。
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15311-6. doi: 10.1073/pnas.93.26.15311.
10
Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function.序列选择性碳水化合物-脱氧核糖核酸相互作用：刺孢霉素低聚糖的二聚体和单体形式干扰转录因子功能。
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):940-4. doi: 10.1073/pnas.93.2.940.
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Biochemistry. 1986 Jun 3;25(11):3296-303. doi: 10.1021/bi00359a032.
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A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin.DNA十二聚体d（CGCAAATTTGCG）的d（A.T）碱基对中的一种分叉氢键构象及其与Distamycin的复合物。
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8385-9. doi: 10.1073/pnas.84.23.8385.
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Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells.分泌型胎盘碱性磷酸酶：一种用于真核细胞基因表达的强大新型定量指标。
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Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically.刺孢霉素γ1I：一种能特异性切割双链DNA的抗肿瘤抗生素。
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Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro.一种人淋巴特异性八聚体结合蛋白（OTF-2）的鉴定与纯化，该蛋白可在体外激活免疫球蛋白启动子的转录。
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