Cargando…

Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical

Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Ling, Zhang, Xiya, Shen, Dongshuai, Yu, Xuezhi, Li, Yuan, Wen, Kai, Shen, Jianzhong, Wang, Zhanhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407904/
https://www.ncbi.nlm.nih.gov/pubmed/32630260
http://dx.doi.org/10.3390/biom10070986
_version_ 1783567713273118720
author Yang, Ling
Zhang, Xiya
Shen, Dongshuai
Yu, Xuezhi
Li, Yuan
Wen, Kai
Shen, Jianzhong
Wang, Zhanhui
author_facet Yang, Ling
Zhang, Xiya
Shen, Dongshuai
Yu, Xuezhi
Li, Yuan
Wen, Kai
Shen, Jianzhong
Wang, Zhanhui
author_sort Yang, Ling
collection PubMed
description Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment. However, achieving this goal is a great challenge, mainly due to the very low molecular weight of FAM. Here, we design two groups of FAM haptens for the first time, maximally exposing the fluorine or amino groups, with the aid of linear aliphatic or phenyl-contained spacer arms. Interestingly, whereas the hapten with fluorine at the far end of the hapten did not induce an antibody response to FAM, the hapten with an amino group at the far end and phenyl-contained spacer arm triggered a significantly specific antibody response. Finally, a monoclonal antibody (mAb) named 5D11 was successfully obtained with an IC(50) value of 97 μg mL(−1) and negligible cross-reactivities to the other nine functional and structural analogs.
format Online
Article
Text
id pubmed-7407904
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74079042020-08-12 Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical Yang, Ling Zhang, Xiya Shen, Dongshuai Yu, Xuezhi Li, Yuan Wen, Kai Shen, Jianzhong Wang, Zhanhui Biomolecules Communication Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment. However, achieving this goal is a great challenge, mainly due to the very low molecular weight of FAM. Here, we design two groups of FAM haptens for the first time, maximally exposing the fluorine or amino groups, with the aid of linear aliphatic or phenyl-contained spacer arms. Interestingly, whereas the hapten with fluorine at the far end of the hapten did not induce an antibody response to FAM, the hapten with an amino group at the far end and phenyl-contained spacer arm triggered a significantly specific antibody response. Finally, a monoclonal antibody (mAb) named 5D11 was successfully obtained with an IC(50) value of 97 μg mL(−1) and negligible cross-reactivities to the other nine functional and structural analogs. MDPI 2020-07-01 /pmc/articles/PMC7407904/ /pubmed/32630260 http://dx.doi.org/10.3390/biom10070986 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Yang, Ling
Zhang, Xiya
Shen, Dongshuai
Yu, Xuezhi
Li, Yuan
Wen, Kai
Shen, Jianzhong
Wang, Zhanhui
Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title_full Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title_fullStr Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title_full_unstemmed Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title_short Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
title_sort hapten design and monoclonal antibody to fluoroacetamide, a small and highly toxic chemical
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407904/
https://www.ncbi.nlm.nih.gov/pubmed/32630260
http://dx.doi.org/10.3390/biom10070986
work_keys_str_mv AT yangling haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT zhangxiya haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT shendongshuai haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT yuxuezhi haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT liyuan haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT wenkai haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT shenjianzhong haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical
AT wangzhanhui haptendesignandmonoclonalantibodytofluoroacetamideasmallandhighlytoxicchemical