Table 1.
Cysteine-reactive probes used in VCF studies
ProbeSpectral propertiesUsage notesExample references
Monobromobimane λex = 394 nm Very small size compared with other probes allows labeling of less accessible locations with lower risk of structural perturbation. Near-UV excitation may cause aberrant photodamage. Islas and Zagotta, 2006; Taraska et al., 2009  
λem = 490 nm 
DPTA-Tb3+ λex = 328 nm Terbium chelate used in LRET studies. Reduced orientation-dependence of energy transfer makes it a more reliable reporter for distance changes than conventional fluorophores. Requires laser excitation in UV range. Cha et al., 1999; Posson et al., 2005  
λem = 492 or 546 nm 
Fluorescein λex = 494 nm Bright, environmentally sensitive fluorescent probe but has pH sensitivity in the physiological range (pKa = 6.4) and is prone to photobleaching. Cha and Bezanilla, 1997; Dempski et al., 2006  
λem = 512 nm 
Alexa Fluor 488 C5 λex = 493 nm Bright fluorescent probe with low pH sensitivity in the physiological range. Lower environmental sensitivity of emission makes it less sensitive to conformational changes in absence of added quenchers. Zheng and Zagotta, 2000; Bruening-Wright et al., 2007  
λem = 516 nm 
Oregon Green λex = 501 nm Derivative of fluorescein with reduced pH sensitivity due to lower pKa (4.6) and lower rate of photobleaching. Emission is highly sensitive to calcium concentrations. Cha and Bezanilla, 1997  
λem = 526 nm 
PyMPO λex = 415 nm Environmentally sensitive probe whose linear shape makes it less bulky than alternatives such as fluorescein or tetramethyl rhodamine. Extended shape means probe reaches far from point of labeling. Savalli et al., 2006; Vaid et al., 2008  
λem = 570 nm 
Tetramethyl rhodamine λex = 548 nm Most commonly used probe with high environmental sensitivity and good photostability. Mannuzzu et al., 1996; Cha and Bezanilla, 1997  
λem = 576 nm 
ProbeSpectral propertiesUsage notesExample references
Monobromobimane λex = 394 nm Very small size compared with other probes allows labeling of less accessible locations with lower risk of structural perturbation. Near-UV excitation may cause aberrant photodamage. Islas and Zagotta, 2006; Taraska et al., 2009  
λem = 490 nm 
DPTA-Tb3+ λex = 328 nm Terbium chelate used in LRET studies. Reduced orientation-dependence of energy transfer makes it a more reliable reporter for distance changes than conventional fluorophores. Requires laser excitation in UV range. Cha et al., 1999; Posson et al., 2005  
λem = 492 or 546 nm 
Fluorescein λex = 494 nm Bright, environmentally sensitive fluorescent probe but has pH sensitivity in the physiological range (pKa = 6.4) and is prone to photobleaching. Cha and Bezanilla, 1997; Dempski et al., 2006  
λem = 512 nm 
Alexa Fluor 488 C5 λex = 493 nm Bright fluorescent probe with low pH sensitivity in the physiological range. Lower environmental sensitivity of emission makes it less sensitive to conformational changes in absence of added quenchers. Zheng and Zagotta, 2000; Bruening-Wright et al., 2007  
λem = 516 nm 
Oregon Green λex = 501 nm Derivative of fluorescein with reduced pH sensitivity due to lower pKa (4.6) and lower rate of photobleaching. Emission is highly sensitive to calcium concentrations. Cha and Bezanilla, 1997  
λem = 526 nm 
PyMPO λex = 415 nm Environmentally sensitive probe whose linear shape makes it less bulky than alternatives such as fluorescein or tetramethyl rhodamine. Extended shape means probe reaches far from point of labeling. Savalli et al., 2006; Vaid et al., 2008  
λem = 570 nm 
Tetramethyl rhodamine λex = 548 nm Most commonly used probe with high environmental sensitivity and good photostability. Mannuzzu et al., 1996; Cha and Bezanilla, 1997  
λem = 576 nm 

DPTA, diethylenetriaminepentaacetic acid; PyMPO, 1-[3-(succinimidyloxycarbonyl)benzyl]-4-[5-(4-methoxyphenyl)-2-oxazolyl]pyridinium bromide.

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