Synthesis and characterization of ruthenium(II)-oligopyridine-peptide conjugates. Interactions of the diasteromeres Δ- and Λ-[Ru(bpy)2 (4-COY-4′-Mebpy)]Cl2 (Y = Gly-Lys1-Lys2CONH2, Lys1-Gly-Lys2CONH2, Lys1-Lys2-GlyCONH2) with the oligonucleotide d(5′-CGCGAATTCGCG-3′)2

Diastereomeric complexes of the general formulae Lambda- and Delta-[Ru(bpy)(2)(4-COY-4'-Mebpy)]Cl-2 where bpy = 2,2'-bipyridine and Y = Gly-Lys(1)-Lys(2)CONH(2), Lys(1)-Gly-Lys(2)CONH(2), Lys(1)-Lys(2)-GlyCONH(2), were synthesized and characterized. The ability of these compounds to bind to the oligonucleotide duplex d(5'-CGCGAATTCGCG-3') was studied with NMR techniques. Complex Lambda-2, Lambda-[Ru(bpy)(2)(4-COLys(1)-Gly-Lys(2)CONH(2)),4'-Mebpy)]Cl-2 (Mebpy = methyl-2,2'-bipyridine), interacts non-specifically causing changes for both complex and oligonucleotide H-1 NMR signals. Both Lambda-1, Lambda-[Ru(bpy)(2)(4-COGly-Lys(1)-Lys(2)CONH(2)),4'-Mebpy)]Cl-2 and Lambda-3, Lambda-[Ru(bpy)(2)(4-COLys(1)-Lys(2)-GlyCONH(2)),4'-Mebpy)]Cl-2, were bound to the oligonucleotide through both lysine aliphatic chains, indicating that the side chains of the sequential lysines create a kind of "clamp" to connect the complex with the oligonucleotide. Complex Delta-1, Delta-[Ru(bpy)(2)(4-COGly-Lys(1)-Lys(2)CONH(2)),4'-Mebpy)]Cl-2, interacts with the oligonucleotide duplex with both lysine side chains in a manner similar to Lambda-1. Delta-2, Delta-[Ru(bpy)(2)(4-COLys(1)-Gly-Lys(2)CONH(2)),4'-Mebpy)Cl-2, interacts with the oligonucleotide with the bipyridine ligands. In addition, the formation of a hydrogen bond between the Gly-NH and the carbonyl groups of the oligonucleotide bases was detected. A completely different binding mode was observed for Delta-3 Delta-[Ru(bpy)(2)(4-COLys(1)-Lys(2)-GlyCONH(2)),4'-Mebpy)]Cl-2, which at a ratio of 1:1 ([Ru]/[nucleotide]) opens the oligonucleotide strands. In addition, participation of all three peptidic NH of Delta-3 in hydrogen bonds was observed. (c) 2013 Elsevier Inc. All rights reserved.