Development of highly sensitive and selective antibodies for the detection of the explosive pentaerythritol tetranitrate (PETN) by bioisosteric replacement

An improved antibody against the explosive pentaerythritol tetranitrate (PETN) was developed. The immunogen was designed by the concept of bioisosteric replacement, which led to an excellent polyclonal antibody with extreme selectivity and immunoassays of very good sensitivity. Compounds such as nitroglycerine, 2,4,6‐trinitrotoluene, 1,3,5‐trinitrobenzene, hexogen (RDX), 2,4,6‐trinitroaniline, 1,3‐dinitrobenzene, octogen (HMX), triacetone triperoxide, ammonium nitrate, 2,4,6‐trinitrophenol and nitrobenzene were tested for potential cross‐reactivity. The detection limit of a competitive enzyme‐linked immunosorbent assay was determined to be around 0.5 µg/l. The dynamic range of the assay was found to be between 1 and 1000 µg/l, covering a concentration range of three decades. This work shows the successful application of the bioisosteric concept in immunochemistry by exchange of a nitroester to a carbonate diester. The antiserum might be used for the development of quick tests, biosensors, microtitration plate immunoassays, microarrays and other analytical methods for the highly sensitive detection of PETN, an explosive frequently used by terrorists, exploiting the extreme difficulty of its detection. Copyright © 2015 John Wiley & Sons, Ltd.

[1]  P. Munson,et al.  Quantitative characterization of hormone receptors , 1980, Cancer.

[2]  Reinhard Niessner,et al.  Dip-and-read test strips for the determination of trinitrotoluene (TNT) in drinking water , 1999 .

[3]  R. Niessner,et al.  Development of a highly sensitive enzyme-immunoassay for the determination of triazine herbicides , 1997 .

[4]  R. Niessner,et al.  002 Determination of triazine herbicides by ELISA — Optimization of enzyme tracer synthesis , 1992 .

[5]  G. Digenis,et al.  Effects of structural variations on the rates of enzymatic and nonenzymatic hydrolysis of carbonate and carbamate esters. , 1992, Journal of pharmaceutical sciences.

[6]  J. Goodpaster,et al.  “Fooling fido”—chemical and behavioral studies of pseudo-explosive canine training aids , 2014, Analytical and Bioanalytical Chemistry.

[7]  B. Hammock,et al.  Hapten design for compound-selective antibodies: ELISAS for environmentally deleterious small molecules , 1998 .

[8]  J. S. Caygill,et al.  Current trends in explosive detection techniques. , 2012, Talanta.

[9]  R. Breslow Concerning carbanion intermediates in elemination reactions , 1964 .

[10]  Robert Wilson,et al.  Electrochemiluminescence enzyme immunoassays for TNT and pentaerythritol tetranitrate. , 2003, Analytical chemistry.

[11]  Yurong Tang,et al.  Hapten Design,Modification and Preparation of Artificial Antigens , 2010 .

[12]  Simone Brogi,et al.  Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors. , 2013, Journal of medicinal chemistry.

[13]  F. Fitzpatrick,et al.  Hapten mimic elicits antibodies recognizing prostaglandin E2. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Hongtao Lei,et al.  Application of computer-assisted molecular modeling for immunoassay of low molecular weight food contaminants: A review. , 2009, Analytica chimica acta.

[15]  Sophie Papst,et al.  Bioisosteres In Medicinal Chemistry , 2016 .

[16]  L. J. Myers,et al.  The scientific foundation and efficacy of the use of canines as chemical detectors for explosives. , 2001, Talanta.

[17]  U. Panne,et al.  Monitoring carbamazepine in surface and wastewaters by an immunoassay based on a monoclonal antibody , 2009, Analytical and bioanalytical chemistry.

[18]  W. Maccrehan,et al.  Development of SRM 2907 trace terrorist explosives simulants for the detection of Semtex and triacetone triperoxide. , 2011, Analytical chemistry.

[19]  Henric Östmark,et al.  Vapor Pressure of Explosives: A Critical Review , 2012 .

[20]  Peter Ertl,et al.  Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization , 2010, Molecular informatics.

[21]  Ross J. Harper,et al.  Identification of dominant odor chemicals emanating from explosives for use in developing optimal training aid combinations and mimics for canine detection. , 2005, Talanta.

[22]  D. Rodbard,et al.  Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. , 1978, The American journal of physiology.

[23]  U. Panne,et al.  A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive Triacetone Triperoxide (TATP) , 2011, Biosensors.

[24]  Michael G. Weller,et al.  Extremely sensitive and selective antibodies against the explosive 2,4,6‐trinitrotoluene by rational design of a structurally optimized hapten , 2012, Journal of molecular recognition : JMR.

[25]  and Steve P. Rannard,et al.  Controlled Synthesis of Asymmetric Dialkyl and Cyclic Carbonates Using the Highly Selective Reactions of Imidazole Carboxylic Esters , 1999 .

[26]  Cloaking cytolytic peptides for liposome-based detection and potential drug delivery. , 2002, Biochimica et biophysica acta.

[27]  William A. MacCrehan,et al.  Characterization of Three Types of Semtex (H, 1A, and 10) , 2010 .

[28]  E. Corey,et al.  Useful procedures for the oxidation of alcohols involving pyridinium dichromate in aprotic media , 1979 .

[29]  B. Hammock,et al.  Strategies for immunoassay hapten design , 1995 .

[30]  Richard G. Smith,et al.  A review of biosensors and biologically-inspired systems for explosives detection. , 2008, The Analyst.

[31]  K. Janda,et al.  Catalytic antibodies: hapten design strategies and screening methods. , 2004, Bioorganic & medicinal chemistry.