|題名: ||DNA sequence-specific recognition of peptides incorporating the HPRK and polyamide motifs|
|作者: ||Chang, Jung-cheng;Yang, Chia-hung;Chou, Ping-yen;Yang, Wan-hsu;Chou, I.-chun;Lu, Ching-tai;Jeng, Kee-ching G;鄭建中;Cheng, Chien chung;Sheh, Leung|
|關鍵詞: ||HPRK motif;Polyamide conjugates;Quantitative DNase I footprinting|
|摘要: ||Three peptide amides, HPRK(Py)4HPRK-NH2 (PyH-12), HPRK(Py)3HPRK-NH2 (PyH-11) and HPRK(Py)2HPRK-NH2 (PyH-10), incorporating two HPRK motifs and various 4-amino-1-methylpyrrole-2-carboxylic acid residues (Py) were synthesized by solid-phase peptide methodology. The binding of these three peptides to a 5′-32P-labeled 158-mer DNA duplex (Watson fragment) and to a 5′-32P-labeled 135-mer DNA duplex (complementary Crick fragment) was investigated by quantitative DNase I footprinting. On the 158-mer Watson strand, the most distinctive DNase I blockages seen with all three peptides occur around positions 105–112 and 76–79, corresponding to the sequences 5′-GAGAAAAT-3′ and 5′-CGGT-3′, respectively. However, on the complementary Crick strand, only PyH-12 strongly discriminates the 5′-TTT-3′ site around positions 108–110 whereas both PyH-11 and PyH-10 have moderate binding around positions 102–112 comprising the sequence 5′-ATTTTCTCCTT-3′. Possible bidentate and single interactions of the side-chain functions and α-amino protons of the peptides with DNA bases are discussed.
Three peptide amides, HPRK(Py)4HPRK-NH2 (PyH-12), HPRK(Py)3HPRK-NH2 (PyH-11) and HPRK(Py)2HPRK-NH2 (PyH-10), were synthesized. On a 5′-32P-labeled 158-mer Watson strand, the most distinctive DNase I footprinting blockages seen with all three peptides occur around sequences 5′-GAGAAAAT-3′ and 5′-CGGT-3′. On the complementary 5′-32P-labeled Crick strand, only PyH-12 strongly discriminates the 5′-TTT-3′ site. Possible interactions of the amino acid side chains of these peptides with DNA bases are discussed.
|關聯: ||Bioorganic and medicinal chemistry 12(1), pp.53-61|