ZP4, an improved neuronal Zn2+ sensor of the Zinpyr family.
A second-generation fluorescent sensor for Zn(2+) from the Zinpyr family, ZP4, has been synthesized and characterized. ZP4 (Zinpyr-4, 9-(o-carboxyphenyl)-2-chloro-5-[2-(bis(2-pyridylmethyl)aminomethyl)-N-methylaniline]-6-hydroxy-3-xanthanone) is prepared via a convergent synthetic strategy developed from previous studies with these compounds. ZP4, like its predecessors, has excitation and emission wavelengths in the visible range ( approximately 500 nm), a dissociation constant (K(d)) for Zn(2+) of less than 1 nM and a high quantum yields (Phi = approximately 0.4), making it well suited for biological applications. A 5-fold fluorescent enhancement is observed under simulated physiological conditions corresponding to the binding of the Zn(2+) cation to the sensor, which inhibits a photoinduced electron transfer (PET) quenching pathway. The metal-binding stereochemistry of ZP4 was evaluated through the synthesis and X-ray structural characterization of [M(BPAMP)(H(2)O)(n)](+) complexes, where BPAMP is [2-(bis(2-pyridylmethyl)aminomethyl)-N-methylaniline]-phenol and M = Mn(2+), Zn(2+) (n = 1) or Cu(2+) (n = 0).
Burdette
Shawn C
SC
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Frederickson
Christopher J
CJ
Bu
Weiming
W
Lippard
Stephen J
SJ
D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D001923:Brain Chemistry; D018360:Crystallography, X-Ray; D005452:Fluoresceins / Q000138:chemical synthesis* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009474:Neurons / Q000737:chemistry*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc / Q000032:analysis*
D005452:Fluoresceins; D005456:Fluorescent Dyes; D015032:Zinc