Tetrapeptides induce selective recognition for G-quadruplexes when conjugated to a DNA-binding platform.
3,6-Bis-peptide acridine and acridone conjugates have been designed and synthesised to selectively interact with G-quadruplex DNA. The ligand properties are peptide sequence dependent, the highest discrimination being obtained with the FRHR tetrapeptide (up to >50-fold specificity). Molecular modeling studies have helped us rationalise the data and suggest that human telomeric quadruplex DNA can readily accommodate tetrapeptides, and furthermore that FRHR contributes to stabilization of the complex by non-bonded interactions within the TTA loop pockets of the quadruplex. These studies indicate that targeting distinct features of a G-quadruplex with hybrid molecules is a promising strategy for discriminating between quadruplex and duplex DNA.
University Chemical Laboratory, University of Cambridge, UK.
Sylvain
S
Ladame
James A
JA
Schouten
John
J
Stuart
Jose
J
Roldan
Stephen
S
Neidle
Shankar
S
Balasubramanian
D000166:Acridines / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011759:Pyrrolidines / Q000737:chemistry
C471713:3,6-bis-(3-pyrrolidinopropionamide)acridine; D000166:Acridines; D010455:Peptides; D011759:Pyrrolidines; D004247:DNA