| Summary: | 碩士 === 東海大學 === 化學系 === 92 === This thesis reports the DNA sequence-specific recognition studies of seven N-methylpyrrole polyamide-peptide conjugates; PyH-12, PyH-11, PyH-10, RPyH-12, PyHK-10, PyHyp-12, RHyp-12 that contain various HPRK motif and various 4-amino-1-methylpyrrole-2-carboxylic acid residues. The binding of these polypeptides to a 5''-32P labeled 158mer Watson strand and to a 5''-32P labeled 135mer Crick strand was investigated by quantitative DNase I footprinting. The footprinting results show that these polypeptides highly prefer sequences comprising four consecutive A residues on the Watson strand and also on the complementary Crick strand consisting of three or four T''s. These results suggest the possibility of bidentate interaction between the side chain of polypeptide and AT base pair. PyH-12 specifically binds to the A/T sequence and also to the G/C sequence at position 76-79, corresponding to the sequence 5''-CGGT-3''. Cooperativity studies disclose the binding mechanism of PyH-12, PyHyp-12, RHyp-12 to the DNA duplex. Temperature dependent effect are also involved. These studies show that the polypeptides which incorporated N-methylpyrrole motif and HPRK motif have augmented sequence specificity of DNA binding processes and without sacrificing binding affinity.
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