combinatorial synthesis, screening, and binding studies of highly functionalized polyamino-amido oligomers for binding to folded rna组合合成、筛选和绑定的研究高度功能化polyamino-amido绑定折叠rna寡聚物.pdfVIP

Hindawi Publishing Corporation Journal of Nucleic Acids Volume 2012, Article ID 971581, 7 pages doi:10.1155/2012/971581 Research Article Combinatorial Synthesis, Screening, and Binding Studies of Highly Functionalized Polyamino-amido Oligomers for Binding to Folded RNA Jonathan K. Pokorski and Daniel H. Appella Laboratory of Bioorganic Chemistry, NIH, NIDDK, Bethesda, MD 20892, USA Correspondence should be addressed to Daniel H. Appella, appellad@ Received 1 June 2012; Revised 28 June 2012; Accepted 29 June 2012 Academic Editor: Eriks Rozners Copyright © 2012 J. K. Pokorski and D. H. Appella. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Folded RNA molecules have recently emerged as critical regulatory elements in biological pathways, serving not just as carriers of genetic information but also as key components in enzymatic assemblies. In particular, the transactivation response element (TAR) of the HIV genome regulates transcriptional elongation by interacting specifically with the Tat protein, initiating the recruitment of the elongation complex. Preventing this interaction from occurring in vivo halts HIV replication, thus making RNA-binding molecules an intriguing pharmaceutical target. Using α-amino acids as starting materials, we have designed and synthesized a new class of polyamino-amido oligomers, called PAAs, specifically for binding to folded RNA structures. The PAA monomers were readily incorporated into a 125-member combinatorial library of PAA trimers. In order to rapidly assess RNA binding, a quantum dot-based fluorescent screen was developed to visualize RNA binding on-resin. The