Abstract
We report the syntheses of chemical building blocks of a particular class of chiral PNAs, called miniPEG-containing (R)-gamma PNAs (or (R)-MPĪ³PNAs). The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of racemization in the alkylation and reductive amination steps. The methodology is general and robust, ideally suited for large-scale monomer productions with most synthetic steps providing excellent chemical yields without the need for purification other than a simple workup and precipitation.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Nielsen PE, Egholm M, Berg RH, Buchardt O (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254(5037):1497ā1500
Nielsen PE (1999) Peptide nucleic acid. A molecule with two identities. Acc Chem Res 32:624ā630
Demidov VV, Potaman VN, Frank-Kamenetskii MD, Egholm M, Buchard O, Sonnichsen SH, Nielsen PE (1994) Stability of peptide nucleic acids in human serum and cellular extracts. Biochem Pharmacol 48(6):1310ā1313
Nielsen PE, Haaima G (1997) Peptide nucleic acid (PNA). A DNA mimic with a pseudopeptide backbone. Chem Soc Rev 26(2):73ā78
Kumar VA, Ganesh KN (2005) Conformationally constrained PNA analogues: structural evolution toward DNA/RNA binding selectivity. Acc Chem Res 38:404ā412
Corradini R, Sforza S, Tedeschi T, Marchelli R (2007) Chirality as a tool in nucleic acid recognition: principles and relevance in biotechnology and in medicinal chemistry. Chirality 19:269ā294
Hyrup B, Egholm M, Buchardt O, Nielsen PE (1996) A flexible and positively charged PNA analog with an ethylene-linker to the nucleobase: synthesis and hybridization properties. Bioorg Med Chem Lett 6:1083ā1088
Hyrup B, Egholm M, Nielsen PE, Wittung P, Norden B, Buchardt O (1994) Structure-activity studies of the binding of modified peptide nucleic acids (PNAs) to DNA. J Am Chem Soc 116(18):7964ā7970
Dragulescu-Andrasi A, Rapireddy S, Frezza BM, Gayathri C, Gil RR, Ly DH (2006) A simple gamma-backbone modification preorganizes peptide nucleic acid into a helical structure. J Am Chem Soc 128:10258ā10267
Rapireddy S, He G, Roy S, Armitage BA, Ly DH (2007) Strand invasion of mixed-sequence B-DNA by acridine-linked, gamma-peptide nucleic acid (gamma-PNA). J Am Chem Soc 129:15596ā15600
Bahal R, Sahu B, Rapireddy S, Lee C-M, Ly DH (2012) Sequence-unrestricted, Watson-Crick recognition of double helical B-DNA by (R)-MiniPEG-gPNAs. Chembiochem 13:56ā60
Sacui I, Hsieh W-C, Manna A, Sahu B, Ly DH (2015) Gamma peptide nucleic acids: as orthogonal nucleic acid recognition codes for organizing molecular self-assembly. J Am Chem Soc 137:8603ā8610
Hsieh W-C, Martinez GR, Wang AH-J, Wu SF, Chamdia R, Ly DH (2018) Stereochemical conversion of nucleic acid circuits via strand displacement. Commun Chem 1:89
Sahu B, Sacui I, Rapireddy S, Zanotti KJ, Bahal R, Armitage BA, Ly DH (2011) Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing g-peptide nucleic acids with superior hybridization properties and water solubility. J Org Chem 76:5614ā5627
Singer A, Rapireddy S, Ly DH, Meller A (2012) Electronic barcoding of a viral gene at the single-molecule level. Nano Lett 12:1722ā1728
Bahal R, McNeer NA, Quijano E, Liu Y, Sulkowski P, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, Lopez-Giraldez F, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock D, Saltzman WM, Ly DH, Glazer PM (2016) In vivo correction of anemia in b-thalassemic mice by yPNA-mediated gene editing with nanoparticle delivery. Nat Commun 7:13304
Ricciadi AS, Bahal R, Farrelly JS, Quijano E, Bianchi AH, Luks VL, Putman R, Lopez-Giraldez F, Coskun S, Song E, Liu Y, Hsieh W-C, Ly DH, Stitelman DH, Glazer PM, Saltzman WM (2018) In utero nanoparticle delivery for site-specific genome editing. Nat Commun 9:2481
Asahina Y, Takei M, Kimura T, Fukuda Y (2008) Synthesis and antibacterial activity of novel pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid derivatives carrying the 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl group as a C-10 substituent. J Med Chem 51:3238ā3249
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Hsieh, WC., Ly, D.H. (2020). A Robust Method for Preparing Optically Pure MiniPEG-Containing Gamma PNA Monomers. In: Nielsen, P. (eds) Peptide Nucleic Acids. Methods in Molecular Biology, vol 2105. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0243-0_2
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0243-0_2
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0242-3
Online ISBN: 978-1-0716-0243-0
eBook Packages: Springer Protocols