مروری بر اسید نوکلئیک پپتیدی: ساختار، خصوصیات و کاربردها

نوع مقاله : Review Article

نویسندگان

1 دانشجوی کارشناسی ارشد، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه بیولوژی مولکولی و علوم تشریح، دانشکده‌ی پزشکی و کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 استادیار، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه بیولوژی مولکولی و علوم تشریح، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

چندین دهه است که موضوع آنالوگ‌های اسید‌های نوکلئیک توجه برخی دانشمندان علم بیولوژی را به خود معطوف نموده است. برخی از این مولکول‌های صناعی به عنوان ابزارهای قدرتمندی در بیولوژی مولکولی و بیوتکنولوژی، مورد توجه ویژه قرار گرفته‌اند. چهار دسته‌ی عمده‌ی این آنالوگ‌های صناعی عبارت از زنونوکلئیک اسید (XNA یا Xeno nucleic acid)، مورفولینو (Morpholino) و اسید نوکلئیک قفل شده (LNA یا Locked nucleic acid) و نوکلئیک اسید پپتیدی (PNA یاPeptide nucleic acid) که دسته‌ی چهارم این آنالوگ‌ها بود و در این میان، جایگاه برجسته‌ای دارد. PNA، پلیمری است از واحدهای ان-آمینو اتیل گلایسین که به هر یک از این واحدها بازهای پورین/ پیریمیدین اتصال یافته است. این پلیمر، خصوصیات پپتیدها و اسیدهای نوکلئیک را توأمان دارد و قادر است به طور اختصاصی به نوکلئیک اسیدهای طبیعی یا PNA‌های دیگر، هیبرید شود که این ویژگی و دیگر خصوصیات ویژه‌ی این مولکول باعث به کارگیری آن در بسیاری از روش‌های بیولوژی مولکولی در زمینه‌ی تشخیص و درمان بیماری‌ها شده است. در این مقاله، ساختار، خصوصیات بیوشیمیایی و کاربردهای زیست پزشکی PNA شرح داده می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

An Overview of Peptide Nucleic Acids: Structure, Properties, and Applications

نویسندگان [English]

  • Aref Farrokhifard 1
  • Majid Kheirollahi 2
1 MSc Student, Pediatrics Inherited Diseases Research Center And Department of Genetics and Molecular Biology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Pediatrics Inherited Diseases Research Center And Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

For decades, nucleic acid analogues have been emerged in molecular biology. Some of these analogues are powerful bimolecular tools in biotechnology. Among the four major classes of these synthetic molecules (XNA: xenonucleic acid, LNA: locked nucleic acid, PNA: peptide nucleic acid and morpholino), PNA is the most important. In PNA, N-aminoethyle glycine units (to which purine/pyrimidine bases have been attached), are joined together to form an achiral and peptide-like structure that mimics the behavior of DNA and can hybridize to nucleic acid and to other PNA in sequence specific manner. Because of its unique physicochemical properties, PNA in many cases prefers over natural oligonucleotide and therefore, have been exploited in some strategies and methods in the field of diagnostics and therapy. In this review, we describe the structure, biochemical properties, and biomedical applications of PNA.

کلیدواژه‌ها [English]

  • Peptide Nucleic Acids
  • Structure
  • Biochemical properties
  • Biomedical applications
  1. Ray A, Norden B. Peptide nucleic acid (PNA): its medical and biotechnical applications and promise for the future. FASEB J 2000; 14(9): 1041-60.
  2. Nielsen PE, Egholm M. An introduction to peptide nucleic acid. Curr Issues Mol Biol 1999; 1(1-2): 89-104.
  3. Nielsen PE. Applications of peptide nucleic acids. Curr Opin Biotechnol 1999; 10(1): 71-5.
  4. Kovacs G, Timar Z, Kupihar Z, Kele Z, Kovacs L. Synthesis and analysis of peptide nucleic acid oligomers using Fmoc/acyl-protected monomers. J Chem Soc Perkin Trans 1 2002; (10): 1266-70.
  5. Jordan S, Schwemler C, Kosch W, Kretschmer A, Stropp U, Schwenner E, et al. New hetero-oligomeric peptide nucleic acids with improved binding properties to complementary DNA. Bioorganic and Medicinal Chemistry Letters 1997; 7(6): 687-90.
  6. Hyrup B, Egholm M, Nielsen PE, Wittung P, Norden B, Buchardt O. Structure-activity studies of the binding of modified peptide nucleic acids (PNAs) to DNA. J Am Chem Soc 1994; 116(18): 7964-70.
  7. Egholm M, Christensen L, Dueholm KL, Buchardt O, Coull J, Nielsen PE. Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Nucleic Acids Res 1995; 23(2): 217-22.
  8. Edrup AB, Dahl O, Nielsen PE. A novel peptide nucleic acid monomer for recognition of thymine in triple-helix structures. J Am Chem Soc. 1997; 119(45): 11116-7.
  9. Griffith MC, Risen LM, Greig MJ, Lesnik EA, Sprankle KG, Griffey RH, et al. Single and Bis peptide nucleic acids as triplexing agents: binding and stoichiometry. J Am Chem Soc 1995; 117(2): 831-2.
  10. Wittung P, Nielsen PE, Buchardt O, Egholm M, Norden B. DNA-like double helix formed by peptide nucleic acid. Nature 1994; 368(6471): 561-3.
  11. Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA, et al. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 1993; 365(6446): 566-8.
  12. Kurakin A, Larsen HJ, Nielsen PE. Cooperative strand displacement by peptide nucleic acid (PNA). Chem Biol 1998; 5(2): 81-9.
  13. Peffer NJ, Hanvey JC, Bisi JE, Thomson SA, Hassman CF, Noble SA, et al. Strand-invasion of duplex DNA by peptide nucleic acid oligomers. Proc Natl Acad Sci U S A 1993; 90(22): 10648-52.
  14. Lohse J, Dahl O, Nielsen PE. Double duplex invasion by peptide nucleic acid: a general principle for sequence-specific targeting of double-stranded DNA. Proc Natl Acad Sci U S A 1999; 96(21): 11804-8.
  15. Pellestor F, Paulasova P. The peptide nucleic acids (PNAs), powerful tools for molecular genetics and cytogenetics. Eur J Hum Genet 2004; 12(9): 694-700.
  16. Nielsen PE, Haaima G, Lohse A, Buchardt O. Peptide nucleic acids (PNAs) containing thymine monomers derived from chiral amino acids: hybridization and solubility properties of d-lysine pna. Angew Chem Int Ed Engl 1996; 35(17): 1939-42.
  17. Hamilton SE, Simmons CG, Kathiriya IS, Corey DR. Cellular delivery of peptide nucleic acids and inhibition of human telomerase. Chem Biol 1999; 6(6): 343-51.
  18. Basu S, Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconjug Chem 1997; 8(4): 481-8.
  19. Faruqi AF, Egholm M, Glazer PM. Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells. Proc Natl Acad Sci U S A 1998; 95(4): 1398-403.
  20. Pooga M, Soomets U, Hallbrink M, Valkna A, Saar K, Rezaei K, et al. Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat Biotechnol 1998; 16(9): 857-61.
  21. Simmons CG, Pitts AE, Mayfield LD, Shay JW, Corey DR. Synthesis and membrane permeability of PNA-peptide conjugates. Bioorganic and Medicinal Chemistry Letters 1997; 7(23): 3001-6.
  22. Koppelhus U, Nielsen PE. Cellular delivery of peptide nucleic acid (PNA). Adv Drug Deliv Rev 2003; 55(2): 267-80.
  23. Nielsen PE, Egholm M, Buchardt O. Sequence-specific transcription arrest by peptide nucleic acid bound to the DNA template strand. Gene 1994; 149(1): 139-45.
  24. Veselkov AG, Demidov VV, Nielson PE, Frank-Kamenetskii MD. A new class of genome rare cutters. Nucleic Acids Res 1996; 24(13): 2483-7.
  25. Demidov VV, Yavnilovich MV, Belotserkovskii BP, Frank-Kamenetskii MD, Nielsen PE. Kinetics and mechanism of polyamide ("peptide") nucleic acid binding to duplex DNA. Proc Natl Acad Sci U S A 1995; 92(7): 2637-41.
  26. Larsen HJ, Nielsen PE. Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: sequence-specific suicide transcription. Nucleic Acids Res 1996; 24(3): 458-63.
  27. Bentin T, Nielsen PE. Enhanced peptide nucleic acid binding to supercoiled DNA: possible implications for DNA "breathing" dynamics. Biochemistry 1996; 35(27): 8863-9.
  28. Hanvey JC, Peffer NJ, Bisi JE, Thomson SA, Cadilla R, Josey JA, et al. Antisense and antigene properties of peptide nucleic acids. Science 1992; 258(5087): 1481-5.
  29. Mollegaard NE, Buchardt O, Egholm M, Nielsen PE. Peptide nucleic acid.DNA strand displacement loops as artificial transcription promoters. Proc Natl Acad Sci U S A 1994; 91(9): 3892-5.
  30. Praseuth D, Grigoriev M, Guieysse AL, Pritchard LL, Harel-Bellan A, Nielsen PE, et al. Peptide nucleic acids directed to the promoter of the alpha-chain of the interleukin-2 receptor. Biochim Biophys Acta 1996; 1309(3): 226-38.
  31. Knudsen H, Nielsen PE. Antisense properties of duplex- and triplex-forming PNAs. Nucleic Acids Res 1996; 24(3): 494-500.
  32. Orum H, Nielsen PE, Jorgensen M, Larsson C, Stanley C, Koch T. Sequence-specific purification of nucleic acids by PNA-controlled hybrid selection. Biotechniques 1995; 19(3): 472-80.
  33. Seeger C, Batz HG, Orum H. PNA-mediated purification of PCR amplifiable human genomic DNA from whole blood. Biotechniques 1997; 23(3): 512-7.
  34. Orum H, Nielsen PE, Egholm M, Berg RH, Buchardt O, Stanley C. Single base pair mutation analysis by PNA directed PCR clamping. Nucleic Acids Res 1993; 21(23): 5332-6.
  35. Thiede C, Bayerdorffer E, Blasczyk R, Wittig B, Neubauer A. Simple and sensitive detection of mutations in the ras proto-oncogenes using PNA-mediated PCR clamping. Nucleic Acids Res 1996; 24(5): 983-4.
  36. Perry-O'Keefe H, Yao XW, Coull JM, Fuchs M, Egholm M. Peptide nucleic acid pre-gel hybridization: an alternative to southern hybridization. Proc Natl Acad Sci U S A 1996; 93(25): 14670-5.
  37. Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little MT, Dirks RW, et al. Heterogeneity in telomere length of human chromosomes. Hum Mol Genet 1996; 5(5): 685-91.
  38. BIAcore X Instrument Handbook Preliminary ed. Uppsala, Sweden: Pharmacia Biosensor AB; 1996.
  39. Wang J, Palecek E, Nielsen PE, Rivas G, Cai X, Shiraishi H, et al. Peptide Nucleic Acid Probes for Sequence-Specific DNA Biosensors. J Am Chem Soc 1996; 118(33): 7667-70.
  40. Demidov V, Frank-Kamenetskii MD, Egholm M, Buchardt O, Nielsen PE. Sequence selective double strand DNA cleavage by peptide nucleic acid (PNA) targeting using nuclease S1. Nucleic Acids Res 1993; 21(9): 2103-7.
  41. Galbiati S, Foglieni B, Travi M, Curcio C, Restagno G, Sbaiz L, et al. Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point for non-invasive prenatal diagnosis of beta-thalassemia. Haematologica 2008; 93(4): 610-4.
  42. Wang G, Xu X, Pace B, Dean DA, Glazer PM, Chan P, et al. Peptide nucleic acid (PNA) binding-mediated induction of human gamma-globin gene expression. Nucleic Acids Res 1999; 27(13): 2806-13.
  43. Koh W. Peptide nucleic acid (PNA) and its applications [Online]. [cited 2013]; Available from: URL: http://panagene.com/eng/bbs/ndata/ pn_ref/pn_ref_1227242202.pdf‎
  44. Taylor RW, Chinnery PF, Turnbull DM, Lightowlers RN. Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids. Nat Genet 1997; 15(2): 212-5.