Lysinyl macrocyclic hexaoxazoles: synthesis and selective G-quadruplex stabilizing properties.
Macrocyclic hexaoxazoles having one or two lysinyl side chains in which the terminal nitrogen is either a primary amine, N,N-dimethylamine, or an acetamide have been synthesized. Sodium ion has been found to be beneficial to the macrocyclization step by acting as a template around which the linear polyoxazole can organize. Each of the targeted compounds selectivity stabilizes G-quadruplex versus duplex DNA. Compounds with one valine and one lysine residue display the best combination of G-quadruplex stabilizing ability with no detectable stabilization of duplex DNA.
Rzuczek
Suzanne G
SG
Department of Pharmaceutical Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Pilch
Daniel S
DS
LaVoie
Edmond J
EJ
Rice
Joseph E
JE
D004247:DNA / Q000187:drug effects*; D015195:Drug Design; D054856:G-Quadruplexes; D008239:Lysine / Q000737:chemistry* / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047028:Macrocyclic Compounds; D010080:Oxazoles; D004247:DNA; D008239:Lysine