Molecular recognition between oligopeptides and nucleic acids. Monocationic imidazole lexitropsins that display enhanced GC sequence dependent DNA binding.
A series of monocationic lexitropsins, or information-reading oligopeptides, were synthesized to minimize and offset the AT bias for doubly cationic ligands bound in the minor groove of DNA. The compounds possess an N-formyl group in place of the guanidinium moiety normally present in netropsin. By systematic replacement of the N-methylpyrrole groups of the dipeptide with N-methylimidazole, a remarkably high degree of sequence specificity was obtained. One of the compounds having two N-methylimidazole residues was found to exhibit dramatically altered specificity when compared with netropsin and preferred to bind to the sequence 5'-CCGT-3' 3'-GGCA-5'. The structural elements underlying sequence recognition in terms of the model for the netropsin-DNA interaction are presented and discussed.
Kissinger
K
K
Department of Chemistry, Syracuse University, New York 13244-1200.
Krowicki
K
K
Dabrowiak
J C
JC
Lown
J W
JW
D001483:Base Sequence; D004247:DNA; D003850:Deoxyribonuclease I; D006146:Guanidines / Q000138:chemical synthesis; D007093:Imidazoles / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009429:Netropsin / Q000031:analogs & derivatives / Q000138:chemical synthesis; D009842:Oligopeptides; D013329:Structure-Activity Relationship
D006146:Guanidines; D007093:Imidazoles; D007202:Indicators and Reagents; D009842:Oligopeptides; C053654:lexitropsin; D009429:Netropsin; D004247:DNA; D003850:Deoxyribonuclease I