Synthesis and hybridization properties of RNA containing 8-chloroadenosine.

Abstract

8-Chloroadenosine (8-Cl-Ado) has shown potential as a chemotherapeutic agent for the treatment of multiple myeloma and certain leukemias. 8-Cl-Ado treatment leads to a decrease in global RNA levels and incorporation of the analog into cellular RNA in malignant cells. To investigate the effects of 8-Cl-Ado modifications on RNA structure and function, an 8-Cl-Ado phosphoramidite and controlled-pore glass support were synthesized and used to introduce 8-Cl-Ado at internal and 3'- terminal positions, respectively. RNA oligonucleotides containing 8-chloroadenine (8-Cl-A) residues were synthesized and hybridized with complementary RNA strands. Circular dichroism spectroscopy of the resulting RNA duplexes revealed that the modified nucleobase does not perturb the overall A-form helix geometry. The thermal stabilities of 8-Cl-Ado modified duplexes were determined by UV thermal denaturation analysis and were compared with analogous natural duplexes containing standard and mismatched base pairs. The 8-Cl-Ado modification destabilizes RNA duplexes by approximately 5 kcal/mole, approximately as much as a U:U mismatched base pair. The duplex destabilization of 8-Cl-A may result from perturbation of Watson-Crick base pairing induced by conformational preferences of 8-halogenated nucleosides.

• Authors: Lisa S Chen, Terry L Sheppard
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 21 Issue 8-9 Pg. 599-617 ( 2002) ISSN: 1525-7770 [Print] United States
• PMID: 12484453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Complementary
• 2-Chloroadenosine
• RNA
• 8-chloroadenosine

Topics

• 2-Chloroadenosine (analogs & derivatives, chemical synthesis, chemistry, radiation effects)
• Circular Dichroism
• Hot Temperature
• Molecular Structure
• Nucleic Acid Denaturation (radiation effects)
• Nucleic Acid Hybridization
• RNA (chemical synthesis, chemistry, radiation effects)
• RNA Stability (radiation effects)
• RNA, Complementary (chemistry)
• Ultraviolet Rays