Fluorescently labeled risedronate and related analogues: "magic linker" synthesis.
We report synthesis of the first fluorescently labeled conjugates of risedronate (1), using an epoxide linker strategy enabling conjugation of 1 via its pyridyl nitrogen with the label (carboxyfluorescein). Unlike prior approaches to create fluorescent bisphosphonate probes, the new linking chemistry did not abolish the ability to inhibit protein prenylation in vitro, while significantly retaining hydroxyapatite affinity. The utility of a fluorescent 1 conjugate in visualizing osteoclast resorption in vitro was demonstrated.
Kashemirov
Boris A
BA
Department of Chemistry, University of Southern California, Los Angeles, California 90089-0744, USA.
Bala
Joy Lynn F
JL
Chen
Xiaolan
X
Ebetino
F H
FH
Xia
Zhidao
Z
Russell
R Graham G
RG
Coxon
Fraser P
FP
Roelofs
Anke J
AJ
Rogers
Michael J
MJ
McKenna
Charles E
CE
D000818:Animals; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010010:Osteoclasts / Q000378:metabolism; D011817:Rabbits; D000068296:Risedronic Acid; D013696:Temperature
D005456:Fluorescent Dyes; D000068296:Risedronic Acid; D012968:Etidronic Acid