An azacrown-functionalized peptide as a metal ion based catalyst for the cleavage of a RNA-model substrate.
The previously synthesized, terminally blocked heptapeptide Ac-Aib-ATANP-Aib-Aib-ATANP-Aib-Aib-OMe (1a), where ATANP is (S)-2-amino-3-[1-(1,4,7-triazacyclononane)]propanoic acid and Aib is alpha-aminoisobutyric acid, which is soluble in neutral water where it largely adopts a 3(10)-helical conformation, has been studied, as bimetallic complex [metal ions: Cu(II), Ni(II), Zn(II)], for the transphosphorylation catalysis of the RNA-model substrate 2-(hydroxypropyl)-p-nitrophenyl phosphate (HPNP). A detailed analysis was carried out with the Zn(II) dinuclear complex. Comparison with the mononuclear Zn(II) complex with 1,4,7-triazacyclononane (3) points to cooperativity between the two Zn(II) ions in the process catalyzed by 1a-2Zn(II). On the contrary, the dinuclear Zn(II) complex of dipeptide Ac-(ATANP)(2)-OMe (2), lacking any ordered conformation, is less active than 3-Zn(II). The kinetic analysis suggests the following: (a) the peptide is conformationally very robust and does not loose activity up to 50 degrees C; (b) the substrate binds to the peptide-Zn(II) complex, although not all modes of complexation allow us to take advantage of the cooperativity between the two metal centers. The maximum rate acceleration estimated at pH 7 for the fully bound substrate is ca. 200-fold compared with the uncatalyzed process.
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University of Trieste, Department of Chemical Sciences, via L. Giorgieri, 1 34127 Trieste, Italy.
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D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D002384:Catalysis; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007700:Kinetics; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009596:Nitrophenols / Q000737:chemistry; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012313:RNA / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D015032:Zinc / Q000737:chemistry
C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; C436488:2-amino-3-(1-(1,4,7-triazacyclononyl))propanoic acid; D006573:Heterocyclic Compounds, 1-Ring; D008670:Metals; D009596:Nitrophenols; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010455:Peptides; C008644:nitrophenylphosphate; D012313:RNA; D015032:Zinc; D000409:Alanine