19th-banner-rev.gif

Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Synthesis of a Disubstituted Purine Analog and its Binding Interactions with Xanthine Phosphoribosyl Transferase (xpt) Riboswitch

RNA has the remarkable ability to form 3-dimensional structures that parallel the structural complexity of proteins. Highly structured RNA molecules present excellent targets for new classes of antibiotics. Riboswitches are folded regions in the untranslated region of mRNA that control gene expression upon binding to small ligands (1). Our lab is involved in the synthesis of guanine analogs with modifications at both the C2 and C6 position of the purine ring. These analogs have the potential of tightly binding to the 5’-untranslated region of xanthine phosphoribosyl transferase (xpt) riboswitch mRNA (2). High-resolution structure of xpt riboswitch shows that there maybe additional binding space (white ovals in the figure below) where it may be possible to add functional groups without significantly disrupting ligand binding to the existing pocket (3). Modification at the C2 and C6 position of the purine ring can facilitate additional H-bonds with nucleotides near the binding pocket of xpt mRNA potentially yielding stronger ligand-mRNA interactions. Current work in our lab is focused on the synthesis and characterization of 2-acetamido-6-hydrazone-purine. Binding affinity of analogs to riboswitch mRNA is tested using in-line probing with P-32 labeled mRNA and an in vivo GFP-based reporter system.



References

  1. W. C. Winkler and R. R. Breaker, Annu. Rev. Microbiol. 59, 487-517 (2005).
  2. J. N. Kim, K. F. Blount, I. Puskarz, J. Lim, K. H. Link, and R. R. Breaker, ACS Chem. Biol. 4, 915 – 927 (2009).
  3. R. T. Batey, S. D. Gilbert, and R. K. Montange, Nature, 432, 411-415 (2004).

Angela Potenza
Rachit Neupane
Emily McLaughlin
Swapan S. Jain

Department of Chemistry
Bard College
Annandale on Hudson, NY 12504

Ph: 845-752-2354
Fx: 845-752-2339
sjain@bard.edu