DNA-small molecule chimera with responsive protein-binding ability.
In this communication, we disclose a generalizable strategy for developing agents with regulable protein-binding ability. In particular, a responsive DNA-small molecule chimera (DC) 1 consisting of two synthetic protein-binding arms and a core oligonucleotide (ODN) domain is discussed. DC 1 can be cycled from a bidentate intramolecular quadruplex form to a monodentate duplex structure, via addition of external ODN stimuli. Importantly, these distinct secondary structures of 1 lead to significantly different protein-binding abilities, with the bidentate conformation showing a 20-fold enhancement (with a 0.8 microM dissociation constant, Kd) in trypsin-binding potency.
Harris
D Calvin
DC
Department of Chemistry, Tulane University, 2015 Percival Stern Hall, New Orleans, Louisiana 70118, USA.
Chu
Xiaozhu
X
Jayawickramarajah
Janarthanan
J
D001550:Benzamidines / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D019793:Fluorescein / Q000737:chemistry; D005454:Fluorescence Polarization; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D010670:Phenylthiourea / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry; D013936:Thymidine / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry
D001550:Benzamidines; D009841:Oligonucleotides; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D010670:Phenylthiourea; D004247:DNA; D019809:Streptavidin; D014357:Trypsin; D002256:Carbonic Anhydrases; C032157:benzamidine; D019793:Fluorescein; D013936:Thymidine