Synthesis and DNA binding properties of 1-(3-aminopropyl)-imidazole-containing triamide f-Im*PyIm: a novel diamino polyamide designed to target 5'-ACGCGT-3'.
A novel diamino/dicationic polyamide f-Im(*)PyIm (5) that contains an orthogonally positioned aminopropyl chain on an imidazole (Im(*)) moiety was designed to target 5'-ACGCGT-3'. The DNA binding properties of the diamino polyamide 5, determined by CD, ΔT(M), DNase I footprinting, SPR, and ITC studies, were compared with those of its monoamino/monocationic counterpart f-ImPyIm (1) and its diamino/dicationic isomer f-ImPy(*)Im (2), which has the aminopropyl group attached to the central pyrrole unit (Py(*)). The results gave evidence for the minor groove binding and selectivity of polyamide 5 for the cognate sequence 5'-ACGCGT-3', and with strong affinity (K(eq)=2.3×10(7) M(-1)). However, the binding affinities varied according to the order: f-ImPy(*)Im (2)>f-ImPyIm (1)≥f-Im(*)PyIm (5) confirming that the second amino group can improve affinity, but its position within the polyamide can affect affinity.
Division of Natural & Applied Sciences and Department of Chemistry, Hope College, 35 East, 12th Street, Holland, MI 49423, USA.
Vijay
V
Satam
Balaji
B
Babu
Alexander
A
Porte
Mia
M
Savagian
Megan
M
Lee
Thomas
T
Smeltzer
Yang
Y
Liu
Joseph
J
Ramos
W David
WD
Wilson
Shicai
S
Lin
Kostantinos
K
Kiakos
John A
JA
Hartley
Moses
M
Lee
D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D020005:Propanols / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C515394:1-(3-aminopropyl)imidazole; D007093:Imidazoles; D020005:Propanols; D011758:Pyrroles; D004247:DNA