DNA sequence-specific recognition of peptides incorporating the HPRK and polyamide motifs

Three peptide amides, HPRK(Py)(4)HPRK-NH2 (PyH-12), HPRK(Py)(3)HPRK-NH2 (PyH-11) and HPRK(Py)(2)HPRK-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'-P-32-labeled 158-mer DNA duplex (Watson fragment) and to a 5'-P-32-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 a-amino protons of the peptides with DNA bases are discussed. (C) 2003 Elsevier Ltd. All rights reserved.