Chemistry Reference
In-Depth Information
bpy
H
4
H
3
H
5
H
5
H
3'
H
6
2
N
H
4'
H
3
C
H
6
2'
4
N
N
H
3
H
5'
m-bpy
2
H
6'
Ru
2+
Lys
His
H
6'
2'
H
5'
H
3'
Gly
N
N
O
O
O
N
N
N
2'
4'
H
6'
H
6
N
H
4'
α
CH
α
CH
α
H
2
N
C
C
C
CH
C
2
H
3'
H
5'
β
C
β
CH
2
O
H
H
H
H
5
H
3
H
4
bpy
γ
C
H
H
H
5
N
3
δ
C
H
H
HN
1
H
2
ε
C
H
H
NH
2
Figure 12.2
Structure of the complex
D
-[Ru(bpy)
2
(m-bpy-GHK)]
2+
with atom numbering
imidazole nitrogen, a peptide nitrogen, the terminal glycyl amino group, and an
oxygen atom from a water molecule.
21,22
In order to investigate its possible sequence specifi city upon DNA binding, N.
Hadjiliadis and collaborators
23,24
conjugated peptide GHK to the
bpy
ligand of the
parent complex [Ru(bpy)
3
]
2+
(bpy = 2,2
- bipyridine) (Figure 12.2 ) which is known
to bind DNA reversibly
25,26
and induce photoactivated cleavage.
27
A
1
H NMR study
of the interaction of the resulting diastereomeric complexes L - and D - [Ru(bpy)
2
(m -
bpy - GHK)]
2+
′
- bipyridine) with two different
DNA sequences, the d(CGCGAATTCGCG)
2
23
and d(CGCGATCGCG)
2
,
24
revealed
that minor changes in the DNA sequence can result in different binding character-
istics. In the case of the system D - [Ru(bpy)
2
(m - GHK)]
2+
- d(CGCGAATTCGCG)
2
1:1, molecular models based on the NOE contacts (Figure 12.3) showed that the D -
isomer bound to the DNA major groove with the two
bpy
ligands oriented towards
the double helix. The L-isomer, on the other hand, approached the DNA minor
groove using the m-bpy ligand placing the lysine
(m - bpy = 4 - carboxy - 4
′
- methyl - 2,2
′
-amino group close to the DNA
phosphates (Figure 12.3).
23
Furthermore, signifi cant chemical shifts of peptide and
cytosine's exocyclic amino group protons, as well as several intermolecular NOEs
demonstrated that the peptide GHK was oriented towards the DNA major groove
close to the central AATT sequence forming possibly specifi c contacts with the
DNA bases. However, no signifi cant interaction was observed for the D - [Ru(bpy)
2
(m -
GHK)]
2+
- d(CGCGATCGCG)
2
system at ratio 1:1. Interestingly, increase of the
metal complex to DNA duplex ratio resulted in binding to the major groove and
strand opening of the DNA duplex. At 2:1 ratio, the majority of the intermolecular
NOEs took place between the peptide Gly-His-Lys and sugar protons located in
the major groove. This observation implied an important role for the peptide upon
ε
