Point of attachment and sequence of immobilized peptide-acridine conjugates control affinity for nucleic acids.
Screening of combinatorial libraries by spatial arraying strategies requires library members to be solid-phase immobilized. However, for nucleic acid ligands that bind via intercalation, immobilization may inhibit binding if the tethering functionality is present at the edge of the heterocyle that approaches the duplex during the binding reaction. We report here a method for immobilizing peptide-acridine conjugates (PACs) via either their C- or their N-terminus, corresponding to functionalization at either the 4- or the 9-position of acridine, respectively, and for assaying the nucleic acid binding properties of the resulting resins. We find that both the amino acid sequence of the PAC as well as its point of attachment to the solid support are important in determining affinity for duplex nucleic acids. These results have implications for the design of future on-bead and microarray-based selections and in understanding the nucleic acid binding of functionalized intercalators.
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, USA.
Coby B
CB
Carlson
Peter A
PA
Beal
D000596:Amino Acids / Q000737:chemistry; D000677:Amsacrine / Q000031:analogs & derivatives* / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*
D000596:Amino Acids; D019151:Peptide Library; D010455:Peptides; D000677:Amsacrine; C022202:9-anilinoacridine; D012313:RNA