title: Cyclic Cationic Peptides Containing Sugar Amino Acids Selectively Distinguishes and Inhibits Maturation of Pre-miRNAs of the Same Family.
abstract: The discovery of microRNAs (miRNAs) has added a new dimension to the gene regulatory networks, making aberrantly expressed miRNAs as therapeutically important targets. Small molecules that can selectively target and modulate miRNA levels can thus serve as lead structures. Cationic cyclic peptides containing sugar amino acids represent a new class of small molecules that can target miRNA selectively. Upon treatment of these small molecules in breast cancer cell line, we profiled 96 therapeutically important miRNAs associated with cancer and observed that these peptides can selectively target paralogous miRNAs of the same seed family. This selective inhibition is of prime significance in cases when miRNAs of the same family have tissue-specific expression and perform different functions. During these conditions, targeting an entire miRNA family could lead to undesired adverse effects. The selective targeting is attributable to the difference in the three-dimensional structures of precursor miRNAs. Hence, the core structure of these peptides can be used as a scaffold for designing more potent inhibitors of miRNA maturation and hence function.
authors.affiliation: 1 Academy of Scientific and Innovative Research (AcSIR) , New Delhi, India .|2 CSIR-Institute of Genomics and Integrative Biology , New Delhi, India .
authors.forename: Smita
authors.initials: S
authors.lastname: Nahar
authors.affiliation: 2 CSIR-Institute of Genomics and Integrative Biology , New Delhi, India .
authors.forename: Debojit
authors.initials: D
authors.lastname: Bose
authors.affiliation: 3 CSIR-Central Drug Research Institute , Lucknow, India .
authors.forename: Sudip
authors.initials: S
authors.lastname: Pal
authors.affiliation: 3 CSIR-Central Drug Research Institute , Lucknow, India .|4 Department of Organic Chemistry, Indian Institute of Science , Bangalore, India .
authors.forename: Tushar Kanti
authors.initials: TK
authors.lastname: Chakraborty
authors.affiliation: 1 Academy of Scientific and Innovative Research (AcSIR) , New Delhi, India .|2 CSIR-Institute of Genomics and Integrative Biology , New Delhi, India .|5 CSIR-National Chemical Laboratory , Pune, India .
authors.forename: Souvik
authors.initials: S
authors.lastname: Maiti
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D002241:Carbohydrates / Q000737:chemistry*; D002412:Cations; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D012322:RNA Precursors / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D002241:Carbohydrates; D002412:Cations; D035683:MicroRNAs; D010456:Peptides, Cyclic; D012322:RNA Precursors