title: Synthesis and DNA/RNA Binding Properties of Conformationally Constrained Pyrrolidinyl PNA with a Tetrahydrofuran Backbone Deriving from Deoxyribose.
abstract: Sugar-derived cyclic β-amino acids are important building blocks for designing of foldamers and other biomimetic structures. We report herein the first synthesis of a C-activated N-Fmoc-protected trans-(2S,3S)-3-aminotetrahydrofuran-2-carboxylic acid as a building block for Fmoc solid phase peptide synthesis. Starting from 2-deoxy-d-ribose, the product is obtained in a 6.7% overall yield following an 11-step reaction sequence. The tetrahydrofuran amino acid is used as a building block for a new peptide nucleic acid (PNA), which exhibits excellent DNA binding affinity with high specificity. It also shows preference for binding to DNA over RNA and specifically in the antiparallel orientation. In addition, the presence of the hydrophilic tetrahydrofuran ring in the PNA structure reduces nonspecific interactions and self-aggregation, which is a common problem in PNA due to its hydrophobic nature.
authors.affiliation: Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330, Thailand.
authors.forename: Pitchanun
authors.initials: P
authors.lastname: Sriwarom
authors.affiliation: Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330, Thailand.
authors.forename: Panuwat
authors.initials: P
authors.lastname: Padungros
authors.affiliation: Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330, Thailand.
authors.forename: Tirayut
authors.initials: T
authors.lastname: Vilaivan
mesh_terms: D032701:Biomimetics; D002264:Carboxylic Acids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003855:Deoxyribose / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry*
chemical_list: C000604491:3-aminotetrahydrofuran-2-carboxylic acid; D002264:Carboxylic Acids; D005663:Furans; D020135:Peptide Nucleic Acids; D011759:Pyrrolidines; C018674:tetrahydrofuran; D003855:Deoxyribose; D012313:RNA; D004247:DNA