Peptide nucleic acid (PNA) is DNA mimic, in which the sugar-phosphate backbone is replaced by polyamide structure. Its basic framework is N- (2- aminoethyl) glycine. PNA has good chemical, physical, and biological properties, such as high stability, strong specificity, not hybridization by nuclease and protease. But it has poor water solubility, low membrane permeability.In this paper, the synthesis of modified peptide nucleic acid is reviewed from the backbone, bases and the linker of backbone and base, which makes PNA have better application prospect.
ZENG Fang, WANG Jian-hua, LIU Chun-dong.
Progress of Synthesis of Modified Peptide Nucleic Acid[J]. Chinese Pharmaceutical Journal, 2015, 50(22): 1936-1945 https://doi.org/10.11669/cpj.2015.22.002
[1] NIELSEN P E, EGHOLM M, BERG R H, et al. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide [J]. Science,1991, 254(5037): 1497-1500. [2] ZHOU S L, XIA M F. Research and application of peptide nucleic acids [J]. Chin Pharm J(中国药学杂志),2006, 41(15): 1124-1128. [3] SHAKEEL S, KARIM S, ALI A. Peptide nucleic acid (PNA) - a review [J]. J Chem Technol Biot,2006, 81(6): 892-899. [4] CHU Z, LIU K L. Peptide nucleic acid(PNA): Synthesis, modifications and applications [J].Chin J Org Chem(有机化学),2005, 25(3): 254-263. [5] DUEHOLM K L, EGHOLM M, BEHRENS C, et al. Synthesis of peptide nucleic-acid monomers containing the 4 natural nucleobases - thymine, cytosine, adenine, and guanine and their oligomerization [J]. J Org Chem,1994, 59(19): 5767-5773. [6] MITRA R, GANESH K N. Aminomethylene peptide nucleic acid (am-PNA): Synthesis, regio-/stereospecific DNA binding, and differential cell uptake of (alpha/gamma,r/s)am-PNA analogues [J]. J Org Chem,2012, 77(13): 5696-5704. [7] HAMZAVI R, MEYER C, METZLER-NOLTE N. Synthesis of a C-linked glycosylated thymine-based PNA monomer and its incorporation into a PNA oligomer [J]. Org Biomol Chem,2006, 4(19): 3648-3651. [8] AGUADO G P, RUA F, BRANCHADELL V, et al. Cyclobutyl-carbonyl substituted PNA: Synthesis and study of a novel PNA derivative [J]. Tetrahedron Asymmetr,2006, 17(17): 2499-2503. [9] SFORZA S, TEDESCHI T, CORRADINI R, et al. Induction of helical handedness and DNA binding properties of peptide nucleic acids (PNAs) with two stereogenic centres [J]. Eur J Org Chem,2007, (35): 5879-5885. [10] HUANG H, JOE G H, CHOI S R, et al. Preparation and determination of optical purity of gamma-lysine modified peptide nucleic acid analogues [J]. Arch Pharm Res,2012, 35(3): 517-522. [11] SAHU B, SACUI I, RAPIREDDY S, et al. Synthesis and characterization of conformationallypreorganized, (r)-diethylene glycol-containing gamma-peptide nucleic acids with superior hybridization properties and water solubility [J]. J Org Chem,2011, 76(14): 5614-5627. [12] PENSATO S, D'ANDREA L D, PEDONE C,et al. New synthetic route to gamma-mercaptomethyl PNA monomers [J]. Synthetic Commun,2008, 38(15): 2499-2506. [13] SUGIYAMA T, IMAMURA Y, DEMIZU Y, et al. Beta-PNA: Peptide nucleic acid (PNA) with a chiral center at the beta-position of the PNA backbone [J]. Bioorg Med Chem Lett,2011, 21(24): 7317-7320. [14] KITAMATSU M, KASHIWAGI T,MATSUZAKI R, et al. Synthesis of a novel pyrrolidine-based peptide nucleic acid that contains tertiary amines in the main chain and its internalization into cells [J]. Chem Lett,2006, 35(3): 300-301. [15] NGAMWIRIYAWONG P, VILAIVAN T. Synthesis and nucleic acids binding properties of diastereomeric aminoethylprolyl peptide nucleic acids (aepPNA) [J]. Nucleos Nucleot Nucl,2011, 30(2): 97-112. [16] HOWARTH N M, RICCI J. Synthesis of N-propynyl analogues of peptide nucleic acid (PNA) monomers and their use in the click reaction to prepare N-functionalized PNAs [J]. Tetrahedron,2011, 67(49): 9588-9594. [17] BROWNE E C, LANGFORD S J, ABBOTT B M. Synthesis and effects of conjugated tocopherol analogues on peptide nucleic acid hybridisation [J]. Org Biomol Chem,2013, 11(39): 6744-6750. [18] SUCHY M, HUDSON R H E. Pyrimidine-fused heterocyclic frameworks based on an N4-arylcytosine scaffold: Synthesis, characterization, and PNA oligomerization of the fluorescent cytosine analogue 5,6-benzopc [J]. J Org Chem,2014, 79(8): 3336-3347. [19] GUHA S, GRAF J, GORICKE B, et al. Nucleobase-caged peptide nucleic acids: PNA/PNA duplex destabilization and light-triggered PNA/PNA recognition [J]. J Pept Sci,2013, 19(7): 415-422. [20] WATANABE T, HOSHIDA T, SAKYO J, et al. Synthesis of nucleobase-caged peptide nucleic acids having improved photochemical properties [J]. Org Biomol Chem,2014, 12(28): 5089-5093. [21] MATARAZZO A, MOUSTAFA M E, HUDSON R H E. 5-(Acridin-9-ylamino)uracil - a hydrolytically labile nucleobase modification in peptide nucleic acid [J]. Can J Chem,2013, 91(12): 1202-1206. [22] GASSER G, BELOUSOFF M J, BOND A M, et al. Facile synthesis and detailed characterization of a new ferrocenyl uracil peptide nucleic acid monomer [J]. J Org Chem,2006, 71(20): 7565-7573. [23] VILAIVAN C, SRINARANG W, YOTAPAN N, et al. Specific recognition of cytosine by hypoxanthine in pyrrolidinyl peptide nucleic acid [J]. Org Biomol Chem,2013, 11(14): 2310-2317. [34] MOUSTAFA M E, HUDSON R H E. An azo-based PNA monomer: Synthesis and spectroscopic study [J]. Nucleos Nucleot Nucl,2011, 30(7-9): 740-751. [25] IMOTO S, SHIMOTAZAWA A, HIROHAMA T, et al. Synthesis of the peptide nucleic acid (PNA) incorporating 2-amino-6-vinylpurine derivative and evaluation of the reactivity [J]. Nucleic Acids Symposium Series,2008, (52): 391-392. [26] ZENGEYA T, LI M, ROZNERS E. PNA Containing isocytidinenucleobase: Synthesis and recognition of double helical RNA [J]. Bioorg Med Chem Lett,2011, 21(7): 2121-2124. [27] BUCHARDT O, EGHOLM M, NIELSEN P E, et al. Peptide nucleic acids: United States, 20060160731A1[P]. 2006-07-20. [28] ZARRA R, MONTESARCHIO D, COPPOLA C, et al. Design, synthesis, and hybridisation of water-soluble, peptoid nucleic acid oligomers tagged with thymine[J]. Eur J Org Chem,2009, (35): 6113-6120. [29] HUANG P C, HSU G J, ZHUANG B R, et al. Novel synthesis of alpha-PNA monomers by U-4CR [J]. Amino Acids,2008, 34(3): 449-453. [30] KITAMATSU M, TAKAHASHI A, OHTSUKI T, et al. Synthesis of pyrrolidine-based oxy-peptide nucleic acids carrying four types of nucleobases and their transport into cytoplasm [J]. Tetrahedron,2010, 66(51): 9659-9666.