Glen Report 21.24: Metallobase Nucleic Acid Modification

Exciting new technologies have emerged from the capability to manipulate oligonucleotides using transition metal coordinating organic ligands covalently linked to DNA. Chelate-ligand modified oligonucleotides have been used for in vivo siRNA imaging,¹ or sequence selective DNA cleavage.² Researchers have prepared metallo-DNA supramolecular assemblies that raise the fascinating possibility of metal-based molecular nano-devices such as molecular scale magnets and wires.^3,4 Metallobases can be used to precisely control modified DNA through the addition (or removal) of a small amount of selected metal ion, which may lead to astonishing advancements in oligonucleotide research. Several groups have already reported exceptionally stable unnatural metallobase pairs using ligand modified oligonucleotides.^5-8

Each unique chelation complex exhibits a distinct character regarding affinity and specificity of metal-ion coordination and interaction with the DNA backbone or nucleobases. 2,2’-Dipicolylamine is a versatile metal-coordinating ligand capable of forming complexes with common metal ions including Zn²⁺, Ni²⁺, Cu²⁺, or Ag⁺.⁹ A tremendous advantage of dipicolylamine is complete compatibility with standard DNA synthesis, cleavage and purification protocols. Other chelating ligands may require nonstandard conditions or additional protection and deprotection steps.

Dipicolylamine-metal complexes have been used for the biochemical detection of phosphate¹⁰ and zinc.¹¹ Kady and Groves used dipicolylamine-Fe²⁺ modified oligonucleotides for the sequence-specific cleavage of a DNA target.¹² Other research groups have proposed using the dipicolylamine ligand for chelation of 99mTc or 188Re for biomolecular imaging and therapy.^13,14 Dipicolylamine modified oligonucleotides may also find exciting and innovative uses for surface or nano-particle functionalization, real-time PCR, DNA microarrays, or antisense therapeutics.

We are pleased to offer 2,2’-dipicolylamine phosphoramidite. This product was manufactured and developed by Syntrix Biosystems Inc. Patents Pending. For Research Use Only.

References:

1. Bartlett, D. W.; Su, H.; Hildebrandt, I. J.; Weber, W. A.; Davis, M. E., Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci U S A 2007, 104, (39), 15549-54.
2. Dreyer, G. B.; Dervan, P. B., Sequence-specific cleavage of single-stranded DNA: oligodeoxynucleotide-EDTA X Fe(II). Proc Natl Acad Sci U S A 1985, 82, (4), 968-72.
3. Tanaka, K.; Tengeiji, A.; Kato, T.; Toyama, N.; Shionoya, M., A discrete self-assembled metal array in artificial DNA. Science 2003, 299, (5610), 1212-3.
4. Shionoya, M.; Tanaka, K., Artificial metallo-DNA: a bio-inspired approach to metal array programming. Curr Opin Chem Biol 2004, 8, (6), 592-7.
5. Weizman, H.; Tor, Y., 2,2’-Bipyridine ligandoside: a novel building block for modifying DNA with intra-duplex metal complexes. J Am Chem Soc 2001, 123, (14), 3375-6.
6. Atwell, S.; Meggers, E.; Spraggon, G.; Schultz, P. G., Structure of a copper-mediated base pair in DNA. J Am Chem Soc 2001, 123, (49), 12364-7.
7. Clever, G. H.; Kaul, C.; Carell, T., DNA--metal base pairs. Angew Chem Int Ed Engl 2007, 46, (33), 6226-36.
8. Müller, J., Metal-ion-mediated base pairs in nucleic acids. Eur. J. Inorg. Chem. 2008, 3749-3763.
9. Martell, A. E., Critical Stability Constants. Plenum Press: New York, 1974.
10. Sakamoto, T.; Ojida, A.; Hamachi, I., Molecular recognition, fluorescence sensing, and biological assay of phosphate anion derivatives using artificial Zn(II)-Dpa complexes. Chem Commun (Camb) 2009, (2), 141-52.
11. Lim, N. C.; Bruckner, C., DPA-substituted coumarins as chemosensors for zinc(II): modulation of the chemosensory characteristics by variation of the position of the chelate on the coumarin. Chem Commun (Camb) 2004, (9), 1094-5.
12. Kady, I. O.; Groves, J. T., Synthesis of Iron-Binding Oligonucleotides and Their Reactions with Single-Stranded DNA. Biorg. Med. Chem. Lett. 1993, 3, 1367-1370.
13. Liu, G.; Dou, S.; He, J.; Vanderheyden, J. L.; Rusckowski, M.; Hnatowich, D. J., Preparation and properties of 99mTc(CO)3+-labeled N,N-bis(2-pyridylmethyl)-4-aminobutyric acid. Bioconjug Chem 2004, 15, (6), 1441-6.
14. Storr, T.; Sugai, Y.; Barta, C. A.; Mikata, Y.; Adam, M. J.; Yano, S.; Orvig, C., Carbohydrate-appended 2,2’-dipicolylamine metal complexes as potential imaging agents. Inorg Chem 2005, 44, (8), 2698-705.

Product Information

2,2'-Dipicolylamine Phosphoramidite has been discontinued.