A novel protein biomarker has been designed with improved sensitivity for detecting the presence of cyanide (CN) many days after exposure. Current testing methods measure CN in whole blood. This is problematic since CN is rapidly metabolized and cleared from this compartment (t 1/2 < 1 hr.); it is common for several half-lives to pass before blood samples are drawn for analysis. Our biomarker is a significant improvement since it broadens the detection range of CN exposure from 1-20 days post exposure. Plasma concentration dictates the rate of CN metabolism and the distribution to tissue. Our scientist's formulated an adduct to this protein that significantly preserves the targeted plasma protein for extended exposure detection. Having the ability to test individuals suspected of CN poisoning is particularly relevant to fire fighters due to their repeated exposure and their subsequent above average heart attack rates following exposure.
Cyanide is a potent neurotoxin, a renowned poison, as well as a terrorist weapon. Exposure to CN is routine because it is ubiquitous in the environment. Cyanides are produced by certain bacteria, fungi and algae and are found in a number of foods and plants. It is the by-product of industrial and residential fires as well as a significant component inhaled by cigarette smoking. However, despite a plethora of studies conducted over the last half century, relatively little is known of the potential adverse health effects in groups that are at risk for above normal exposure.
Prior studies by us showed the potential of Cys-SCN human serum albumin (HSA) adducts formed by reaction of CN with susceptible protein disulfides that act as retrospective surrogates of CN exposure. We have since discovered a HSA-SCN adduct at C-terminal Cys567 that is detectable in variable amounts in all samples tested. Base catalysis in the presence of guanidine hydrochloride releases a readily detectable, uniquely modified, C-terminal-19 mer peptide from Cys567– SCN moieties. Inclusion of an internal serum standard containing HSA labeled with 13C15 N at Cys567 and detection using LC-MS/Selective Resonance Monitoring (SRM) permits quantitation of endogenous Cys567 –SCN with high sensitivity and precision. Reaction of CN in vitro with HSA at the Cys558 Cys567 disulfide is specific, rapid, and concentration dependent within the putative physiologically relevant range, demonstrating its potential as a stable biomarker for CN exposure.
- Emergency response workers such as firefighters and EMS personnel
- Military personnel exposed to terrorist weapons
- Research applications for military, fire fighters and EMS
- Assessment of current protective devices and clothing
- Broad detection range from 1-20 days
- Measurement of long-term low levels of exposure
Analysis of cyanide adduct at human serum albumin disulfide 558Cys-567Cys
State of Development:
Early research stage with protein biomarker available
HRI is interested in commercial partners to assist with experimental feedback, to evaluate its potential for large-scale applications, and to assess its value for licensing.
Michael J. Fasco, Ph.D.
Charles R. Hauer III, Ph.D.
Fasco, Michael J., Stack, Robert F., Lu, Shijun, Hauer III, Charles R., Scheider, Erasmus, Dailey, Michael, and Aldous, Kenneth M. Unique Cyanide Adduct in Human Serum Albumin: Potential as a Surrogate Exposure Marker. Chem. Res. Toxicol. 2010, ASAP Publication Date (Web): March 2, 2011 (Article) DOI:10.1021/tx100344e
Fasco, Michael J., Hauer III, Charles R., Stack, Robert F., O'Hehir, Colleen, Barr, John R., and Eadon, George A., Cyanide Adducts with Human Plasma Proteins: Albumin as a Potential Exposure Surrogate Chem. Res. Toxicol. 2007, vol. 20, No 4, 677-684
Presentation at Mass Spectrometry Applications to the Clinical Laboratory February 9, 2010 in San Diego, CA. https://www.msacl.org/msacl_conference2010.php
Diane L. Borghoff, B.S., M.S.
Marketing & Licensing Associate – Intellectual Property
Health Research, Inc.
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