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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

Synthesis of α-(R)-/γ-(S)-Dimethyl Substituted Peptide Nucleic Acid Submonomer Using Mitsunobu Reaction

Author(s): Ahmed S. Abdelbaky, Ivan A. Prokhorov, Igor P. Smirnov, Kristina M. Koroleva, Vitaliy I. Shvets and Yulia G. Kirillova*

Volume 16, Issue 5, 2019

Page: [437 - 446] Pages: 10

DOI: 10.2174/1570178616666190118155031

Price: $65

Abstract

One of the major challenges facing modern biochemical and biomedical technologies are finding molecular tools for diagnosis and detection of genetic diseases. In this connection, several classes of oligonucleotides have been developed that can recognize and bind to DNA and RNA with high affinity and sequence selectivity and withstand enzymatic degradation by proteases and nucleases; however, few can traverse the cell membrane on their own. One such promising class of nucleic acid mimics developed in the last two decades which showed good results in vitro, are the peptide nucleic acids (PNAs). New chiral α- and γ-peptide Nucleic Acid (PNA) submonomer with methyl substituents in pseudopeptide backbone were synthesized via Mitsunobu reaction. The α-(R)-/γ-(S)-configuration of the chiral centres will ensure the preorganization of the PNA oligomer into a right-handed helix. The results obtained showed that Boc/Fmoc-submonomer compatible with Boc-protocol PNAs solid-phase synthesis on an MBHA resin. We synthesized simple and efficient α-R-, γ-S-disubstituted PNA submonomer based on L-Ala and D-Ala with the construction of the intermediate pseudopeptide moiety by Mitsunobu reaction for subsequent use in the Boc-Protocol of solid phase PNA synthesis.

Keywords: Chiral PNA, solid-phase synthesis, submonomeric strategy, PNA, Mitsunobu reaction, nucleic acid.

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[1]
Nielsen, P.E.; Egholm, M.; Berg, R.H.; Buchardt, O. Science, 1991, 254, 1497-1500.
[2]
Demidov, V.V.; Potaman, V.N.; Frank-Kamenetskil, M.D.; Egholm, M.; Buchard, O.; Sönnichsen, S.H. Biochem. Pharmacol., 1994, 48, 1310-1313.
[3]
Egholm, M.; Buchardt, O.; Christensen, L.; Behrens, C.; Freier, S.M.; Driver, D.A.; Berg, R.H.; Kim, S.K.; Norden, B.; Nielsen, P.E. Nature, 1993, 365, 566-568.
[4]
Myers, C.P.; Williams, M.E. Coord. Chem. Rev., 2010, 254, 2416-2428.
[5]
Corradini, R.; Sforza, S.; Tedeschi, T.; Totsingan, F.; Manicardi, A.; Marchelli, R. Curr. Top. Med. Chem., 2011, 11, 1535-1554.
[6]
Sugiyama, T.; Kittaka, A. Molecules, 2012, 18, 287-310.
[7]
Varizhuk, A.M.; Dezhenkov, A.V.; Kirillova, Y.G. Stud. Nat. Prod. Chem., 2016, 47, 261-305.
[8]
Sahu, B.; Chenna, V.; Lathrop, K.L.; Thomas, S.M.; Zon, G.; Livak, K.J.; Ly, D.H. J. Org. Chem., 2009, 74, 1509-1516.
[9]
Dragulescu-andrasi, A.; Rapireddy, S.; Frezza, B.M.; Gayathri, C.; Gil, R.R.; Ly, D.H. J. Am. Chem. Soc., 2006, 128, 10258-10267.
[10]
Mitra, R.; Ganesh, K.N. J. Org. Chem., 2012, 77, 5696-5704.
[11]
Kirillova, Y.; Boyarskaya, N.; Dezhenkov, A.; Tankevich, M.; Prokhorov, I.; Varizhuk, A.; Eremin, S.; Esipov, D.; Smirnov, I.; Pozmogova, G. PLoS One, 2015, 10, e0140468.
[12]
Sforza, S.; Tedeschi, T.; Corradini, R.; Marchelli, R. Eur. J. Org. Chem., 2007, 2007, 5879-5885.
[13]
Tedeschi, T.; Sforza, S.; Corradini, R.; Marchelli, R. Tetrahedron Lett., 2005, 46, 8395-8399.
[14]
Calabretta, A.; Tedeschi, T.; Corradini, R.; Marchelli, R.; Sforza, S. Tetrahedron Lett., 2011, 52, 300-304.
[15]
Calabretta, A.; Tedeschi, T.; Di Cola, G.; Corradini, R.; Sforza, S.; Marchelli, R. Mol. Biosyst., 2009, 5, 1323-1330.
[16]
Sforza, S.; Tedeschi, T.; Calabretta, A.; Corradini, R.; Camerin, C.; Tonelli, R.; Pession, A.; Marchelli, R. Eur. J. Org. Chem., 2010, 13, 2441-2444.
[17]
Corradini, R.; Di Silvestro, G.; Sforza, S.; Palla, G.; Dossena, A.; Nielsen, P.E.; Marchelli, R. Tetrahedron Asymmetry, 1999, 10, 2063-2066.
[18]
Richter, L.S.; Zuckermann, R.N. Bioorg. Med. Chem. Lett., 1995, 5, 1159-1162.
[19]
Sforza, S.; Tedeschi, T.; Corradini, R.; Ciavardelli, D.; Dossena, A.; Marchelli, R. Eur. J. Org. Chem., 2003, 2003, 1056-1063.
[20]
Tedeschi, T.; Sforza, S.; Maffei, F.; Corradini, R.; Marchelli, R. Tetrahedron Lett., 2008, 49, 4958-4961.
[21]
Abdel-Magid, A.F.; Carson, K.G.; Harris, B.D.; Maryanoff, C.A.; Shah, R.D. J. Org. Chem., 1996, 61, 3849-3862.
[22]
Manna, A.; Rapireddy, S.; Sureshkumar, G.; Ly, D.H. Tetrahedron, 2015, 71, 3507-3514.
[23]
Falkiewicz, B.; Kołodziejczyk, A.S.; Liberek, B.; Wiśniewski, K. Tetrahedron, 2001, 57, 7909-7917.
[24]
Christensen, L.; Fitzpatrick, R.; Gildea, B.; Petersen, K.H.; Hansen, H.F.; Koch, T. J. Pept. Sci., 1995, 1, 175-183.
[25]
Lyanov, M.A.; Prokhorov, D.I.; Kirillova, Yu.G.; Lyutik, A.I.; Esipova, O.V.; Shvets, V.I. J. Fine Chem. Technol., 2010, 5, 104-108.
[26]
Shiraishi, T.; Hamzavi, R.; Nielsen, P.E. Nucleic Acids Res., 2008, 36, 4424-4432.
[27]
Dezhenkov, A.V.; Cheshkov, D.A.; Prokhorov, I.A.; Dezhenkova, L.G.; Shvets, V.I.; Kirillova, Y.G. Russ. Chem. Bull., 2015, 5, 1100-1106.
[28]
Dezhenkov, A.V.; Tankevich, M.V.; Nikolskaya, E.D.; Smirnov, I.P.; Pozmogova, G.E.; Shvets, V.I.; Kirillova, Yu.G. Mendeleev Commun., 2015, 25, 47-48.
[29]
Kaiser, E.; Colescott, R.L.; Bossinger, C.D.; Cook, P.I. Anal. Biochem., 1970, 34, 595-598.

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