TY - JOUR
T1 - Synthesis of bis-indole carboxamides as G-quadruplex stabilizing and inducing ligands
AU - Dash, J
AU - Das, R N
AU - Hegde, N
AU - Pantoș, G Dan
AU - Shirude, P S
AU - Balasubramanian, S
PY - 2012/1/9
Y1 - 2012/1/9
N2 - The design and synthesis of a series of bis-indole carboxamides with varying amine containing side chains as G-quadruplex DNA stabilising small molecules are reported. Their interactions with quadruplexes have been evaluated by means of Forster resonance energy transfer (FRET) melting analysis, UV/Vis spectroscopy, circular dichroism spectroscopy and molecular modelling studies. FRET analysis indicates that these ligands exhibit significant selectivity for quadruplex over duplex DNA, and the position of the carboxamide side chains is of paramount importance in G-quadruplex stabilisation. UV/Vis titration studies reveal that bis-indole ligands bind tightly to quadruplexes and show a three- to fivefold preference for c-kit2 over h-telo quadruplex DNA. CD studies revealed that bis-indole carboxamide with a central pyridine ring induces the formation of a single, antiparallel, conformation of the h-telo quadruplex in the presence and absence of added salt. The chirality of h-telo quadruplex was transferred to the achiral ligand (induced CD) and the formation of a preferred atropisomer was observed.
AB - The design and synthesis of a series of bis-indole carboxamides with varying amine containing side chains as G-quadruplex DNA stabilising small molecules are reported. Their interactions with quadruplexes have been evaluated by means of Forster resonance energy transfer (FRET) melting analysis, UV/Vis spectroscopy, circular dichroism spectroscopy and molecular modelling studies. FRET analysis indicates that these ligands exhibit significant selectivity for quadruplex over duplex DNA, and the position of the carboxamide side chains is of paramount importance in G-quadruplex stabilisation. UV/Vis titration studies reveal that bis-indole ligands bind tightly to quadruplexes and show a three- to fivefold preference for c-kit2 over h-telo quadruplex DNA. CD studies revealed that bis-indole carboxamide with a central pyridine ring induces the formation of a single, antiparallel, conformation of the h-telo quadruplex in the presence and absence of added salt. The chirality of h-telo quadruplex was transferred to the achiral ligand (induced CD) and the formation of a preferred atropisomer was observed.
UR - http://www.scopus.com/inward/record.url?scp=84855297344&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1002/chem.201102556
U2 - 10.1002/chem.201102556
DO - 10.1002/chem.201102556
M3 - Article
SN - 0947-6539
VL - 18
SP - 554
EP - 564
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 2
ER -