Structural Studies Applications

Structural Studies Applications

Halogenated bases, cross-linkers, and intercalators all can be used as modifications in oligos slated for use in nucleic acid and protein-nucleic acid structural studies. Details for these types of modifications are provided in the introduction and applications sections of the relevant modification category. Several other modifications can also be used in structural work. For example, selective incorporation of etheno-dA, a highly fluorescent derivative of dA, into DNA or RNA oligos can be particularly useful in structure-function studies of RNA, RNA-protein complexes, and the mechanism of base excision repair (BER) of alkylated DNA damage (1,2). Also, since exocyclic etheno dA adducts likely play an important role in carcinogenesis, etheno-dA-modified oligos can be used as research tools for the study of carcinogenesis in various tissues (3). Another example is N4-Et-dC-modified oligos, which have been used in structure-function studies of better understand how CpG-containing oligos stimulate the innate immune system, and which structural elements in cytosine and guanine bases are required for recognition of, and interaction with, protein/receptor factors responsible for immunostimulation (4).

References

(1) Srivastava, S.C., Raza, S.K., Misra, R. 1,N6-etheno deoxy and ribo adenoGine and 3,N4-etheno deoxy and ribo cytidine phosphoramidites. Strongly fluorescent structures for selective introduction in defined sequence DNA and RNA molecules. Nucleic Acids Res. (1994), 22: 1296-1304.
(2) Dosanjh, M.K., Roy, R., Mitra, S., Singer, B. 1, N6-ethenoadenine is preferred over 3-methyladenine as substrate by a cloned human N-methylpurine-DNA glycosylase (3-methyladenine-DNA glycosylase). Biochemistry (1994), 33: 61624-1628.
(3) Chung, F-L., Chen, H-J.C., Nath, R.G. Lipid peroxidation as a potential endogenous source for the formation of exocyclic DNA adducts. Carcinogenesis (1996), 17: 2105-2111.
(4) Kandimalla, E.R., Yu, D., Zhao, Q., Agrawal, S. Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships. Bioorg. Med. Chem. (2001), 9: 807-813.