| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Detailed solution structures of two catalysis, which we have find to hydrolyze RNA very efficiently under neutral aqueous solution, were examined ; (Zn (II))_2-L1 (1) (L1=N, N, N^1, N-tetrakis (2-pyridylmethyl) -1, 3-diamino-2-propanol and (Zn (II))_2-L2 (2) (L2=N, N, N^1, N-tetrakis (2-pyridylmenthyl) -1, 3-bis (aminomethl) benzene. L1 and L2 differ only in the structure of the linker moiety, which connects two bis (2-pyridylmethyl) amine units. The rate constants for the RNA hydrolysis by two complexes showed quite different pH profiles from rach other, which can be attributed to their very different solution structures. Because acid-base co-catalysis is strongly suggested only for the complex 2, new dinuclear zinc (II) complexes, having similar structures to the complex 2 but the two zinc (II) is in the unequivalent environment, were disigned. (Zn (II))_2-L3 (L3=N- (2-aminoethyl)-N, N^1, N-tris (2-pyridylmethlyl) -1, 3-bis (aminomethyl) benzene) and (Zn (II))_2-L4 (L4=N- (2-hydroxylethyl) -N, N^1, N-tris (2-pyridylmethyl)-1, 3-bis (aminomethyl) benzene). It was found that, on the basis of these molecular design, acidity of coordinated water molecules could be regukated, and, therefore, the catalytic properties of zinc (II) complexes as RNases could also be regulated. On the other hand, peptide hydrolyses under mild conditions were found to be promoted very efficiently, by the cooperationof an internal hydroxy group in the serine residue and a metal ion (zinc (II), cadmium (II), copper (II) or their complexes). The effect of the solvent and the kind of the metal ion on the reaction were studied. Highly sequence-specific hydrolysis of peptide was found to be achieved by choosing an appropriate solvent.
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