Design, synthesis, and biological evaluation of BODIPY-erythromycin probes for bacterial ribosomes.
BODIPY-erythromycin probes of bacterial ribosomes were designed and synthesized by attaching a BODIPY fluorophore to the 4''- and 9-positions of the erythromycin structure. The probes exhibited excellent binding affinity to bacterial ribosomes and competed with erythromycin and other drugs whose binding sites are in the same vicinity of the 50S subunit. The synthetic fluorescent probe 5 was successfully adapted in our ultra high-throughput screening (uHTS) to identify novel ribosome inhibitors.
Li
Jing
J
Department of Medicinal Chemistry, Cumbre Inc., 1502 Viceroy Dr., Dallas, TX 75235, USA.
Kim
In Ho
IH
Roche
Eric D
ED
Beeman
Doug
D
Lynch
A Simon
AS
Ding
Charles Z
CZ
Ma
Zhenkun
Z
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004917:Erythromycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008968:Molecular Conformation; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000900:Anti-Bacterial Agents; D001896:Boron Compounds; D015335:Molecular Probes; D004917:Erythromycin