IBX-4041, A Chromogenic Substrate of Neuraminidases (Sialidases)
Synthesis of IBX-4041 and its application in detection of neuraminidases (sialidases) are documented in 2000 by Jonson at el.1 This compound is a glycoside containing N-acetylneuraminic acid and thymolphthalein units, which are linked together by a glycosidic bond.
IBX-4041 is considered a chromogenic substrate since it displays color change upon hydrolysis by the enzymes, namely neuraminidases.
In the absence of neuraminidases, the solution of IBX-4041 is colorless in neutral and turns yellow when adjusted to basic (pH≥11.0). In the presence of neuraminidases, IBX-4041 is readily hydrolyzed in slightly acidic condition. The enzymatic hydrolysis frees thymolphthalein, which is a pH indicator and displays blue color upon basification (pH≥11.0). Therefore the neuraminidase level of a specific sample can be measured by incubation with an appropriate concentration of IBX-4041, followed by adding a base to the reaction solution. The procedure can be further illustrated by the scheme shown below:
The yellow, green or blue color of the resulting solution respectively indicates low, medium or high level of neuraminidases in the sample being examined. Quantitation of the neuraminidase concentration can also be made by applying this procedure in combination of a colorimeter.
Elevated level of neuraminidases is closely associated with bacterial vaginosis (BV).2 Testing kits that contain IBX-4041 as the active ingredient are sensitive and reliable tools to determine the neuraminidase level. These kits are widely utilized for clinical research and diagnosis of BV. Among currently marketed products, BVBlue3,4 is a well-known example.
LHE Bioscience, Inc. employs carefully designed methodologies to synthesize and purify IBX-4041 and thus insures its quality. Using IBX-4041 free of pigments has proven to be key to making testing kits with high sensitivity and reliability.
1. S Johnson et al., Chromogenic substrates of sialidase and methods of making and using the same, US6512100B1.
2. A M Briselden, B J Moncla, C E Stevens, and S L Hillier, Sialidases (neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora, J. Clin. Microbiol. 1992, 30(3): 663–6.
3. K993732.pdf – US Food and Drug Administration Document.
4. L. Myziuk, B Romanowski, and S Johnson,J. Clin. Microbiol. 2003, 41(5): 1925–28.
Summarized by Scientists of LHE Bioscience, Inc.