title: Preorganized bis-zinc phosphodiester cleavage catalysts possessing natural ligands: a lesson pertinent to bimetallic artificial enzymes.
abstract: Two preorganized bis-zinc receptors (2 and 3) were synthesized wherein the metals were ligated with ligands present in natural phosphodiesterases: imidazoles and carboxylates. The intrametallic distance is near 4.5 A, that found in natural nucleases and other successful artificial nucleases. With only two imidazoles (2), the zinc binding affinities were not high enough to achieve cooperativity. Yet, with a third ligand, a carboxylate (3), cooperativity was found in the cleavage of HPNPP. The preorganization of 3 was achieved using a "steric gearing" strategy. The enhancement was 80-fold for cooperation between the two metals relative to a mono-metallic analogue (5). However, there was no observable enhancement in the hydrolysis of RNA using 3 relative to 5. Therefore, we conclude that placing two zinc atoms that are ligated with natural ligands at the appropriate distance for catalysis is not sufficient to enhance the cleavage of RNA, but is successful for activated RNA substrate mimics.
authors.affiliation: Department of Chemistry and Biochemistry The University of Texas at Austin Austin, TX 78712, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Worm
authors.forename: Feiya
authors.initials: F
authors.lastname: Chu
authors.forename: Kazunari
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Michael D
authors.initials: MD
authors.lastname: Best
authors.forename: Vincent
authors.initials: V
authors.lastname: Lynch
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D002384:Catalysis; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D007093:Imidazoles; D008024:Ligands; D009942:Organometallic Compounds; D012313:RNA; D010727:Phosphoric Diester Hydrolases; D015032:Zinc