title: A systematic study of the features critical for designing a high avidity multivalent aptamer.
abstract: Macromolecular interactions are central to the regulation and execution of many key biological processes, and therefore, they are attractive targets for drug discovery. Previously, we identified an RNA aptamer for the heat shock factor (HSF1), which is capable of interfering with the binding of HSF1 to its cognate DNA elements. Here we report the significant enhancement of avidity through dimerization of this aptamer. In particular, we describe the effect of 2 factors in designing a multivalent aptamer: the distance between active subunits and the flexibility of the linkage.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
authors.forename: Xiaoching
authors.initials: X
authors.lastname: Zhao
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
authors.forename: Hua
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D052157:Aptamers, Nucleotide; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C067168:HSF1 protein, S cerevisiae; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C053134:Hsf protein, Drosophila; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA
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