journal article·2025-01-28Open access

Substructure-Specific Antibodies Against Fentanyl Derivatives

Asheley Chapman, Minghao Xu, Michelle Schroeder, Jason M. Goldstein, Asiya Chida, Joo R. Lee, Xiaoling Tang, Rebekah E. Wharton, M. G. Finn

ACS Nano· Volume 19· Issue 3

Abstract

Structural variants of the synthetic opioid fentanyl are a major threat to public health. Following an investigation showing that many derivatives are poorly detected by commercial lateral flow and related assays, we created hapten conjugate vaccines using an immunogenic virus-like particle carrier and eight synthetic fentanyl derivatives designed to mimic the structural features of several of the more dangerous analogues. Immunization of mice elicited strong antihapten humoral responses, allowing the screening of hundreds of hapten-specific hybridomas for binding strength and specificity. A panel of 13 monoclonal IgG antibodies were selected, each showing a different pattern of recognition of fentanyl structural variations, and all proving to be highly efficient at capturing parent fentanyl compounds in competition ELISA experiments. These results provide antibody reagents for assay development as well as a demonstration of the power of the immune system to create binding agents capable of both broad and specific recognition of small-molecule targets.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Neuropeptides and Animal Physiology · Inhalation and Respiratory Drug Delivery · Nicotinic Acetylcholine Receptors Study

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr., Atlanta, Georgia 30332, United States

Immunodiagnostic Development Team, Preparedness, Response, & Outbreak Services Branch, Division of Core Laboratory Services & Response, Office of Laboratory Systems and Response, Centers for Disease Control and Prevention, 1600 Clifton Rd NE., Atlanta, Georgia 30333, United States

Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy, Atlanta, Georgia 30341, United States

School of Biological Sciences, Georgia Institute of Technology, 901 Atlantic Dr. Atlanta, Georgia 30332, United States

Funding

Centers for Disease Control and Prevention · National Institute of Allergy and Infectious Diseases

References (75)

Show source-provided references
1. 10.1001/jama.2020.1747710.1001/jama.2020.17477 ↗
2. Spencer, M. R. M. A. M.; Warner, M. Drug Overdose Deaths in the United States, 2001–2021. NCHS Data Brief, no. 457; National Center for Health Statistics: Hyattsville, MD, 2022.10.15620/cdc:122556 ↗
3. Centers for Disease Control and Prevention. State Unintentional Drug Overdose Reporting System (SUDORS). Final Data. US Department of Health and Human Services, CDC, Atlanta, GA; October 30. 2023. access at: https://www.cdc.gov/drugoverdose/fatal/dashboard.
4. 10.1001/jama.2018.284410.1001/jama.2018.2844 ↗
5. Van Bever W. F. · Arzneim.-Forsch. · 1976 · 26 · 1548
6. Niemegeers C. · Arzneim.-Forsch. · 1976 · 26 · 1551
7. 10.1111/j.1476-5381.1952.tb01313.x10.1111/j.1476-5381.1952.tb01313.x ↗
8. 10.1016/j.jclinane.2015.08.01010.1016/j.jclinane.2015.08.010 ↗
9. European Monitoring Centre for Drugs and Drug Addiction Report on the Risk Assessment of Methyl 1-(2-Phenylethyl)-4-[phenyl(propanoyl)amino]piperidine-4-Carboxylate (Carfentanil) in the Framework of the Counsil Decision on New Psychoactive Substances; Risk Assessments; Publications Office of the European Union: Luxembourg, 2018.
10. 10.1016/j.neuropharm.2017.10.01610.1016/j.neuropharm.2017.10.016 ↗
11. 10.1007/s11524-018-00343-z10.1007/s11524-018-00343-z ↗
12. 10.1016/j.drugalcdep.2023.11081910.1016/j.drugalcdep.2023.110819 ↗
13. 10.1111/add.1631810.1111/add.16318 ↗
14. See also DEA Laboratory Testing Reveals that 6 out of 10 Fentanyl-Laced Fake Prescription Pills Now Contain a Potentially Lethal Dose of Fentanyl″, https://www.dea.gov/alert/dea-laboratory-testing-reveals-6-out-10-fentanyl-laced-fake-prescription-pills-now-contain (accessed Dec 21, 2024).
15. 10.1016/j.toxlet.2006.05.00710.1016/j.toxlet.2006.05.007 ↗
16. 10.1021/acschemneuro.0c0006410.1021/acschemneuro.0c00064 ↗
17. 10.1016/j.drugpo.2020.10306510.1016/j.drugpo.2020.103065 ↗
18. 10.1093/jat/bkaa18110.1093/jat/bkaa181 ↗
19. Centers for Disease Control and Prevention (CDC) · MMWR Morb. Mortal. Wkly. Rep. · 2008 · 57 · 793
20. O’Connor, S. Fentanyl: China’s Deadly Export to the United States; US-China Economic and Security Review Commission, Staff Research Report, 2017.
21. 10.1016/j.forsciint.2010.07.02210.1016/j.forsciint.2010.07.022 ↗
22. 10.1039/D0TB01509A10.1039/D0TB01509A ↗
23. 10.1111/1556-4029.1463110.1111/1556-4029.14631 ↗
24. 10.1016/j.drugalcdep.2018.06.02010.1016/j.drugalcdep.2018.06.020 ↗
25. 10.1016/j.forsciint.2019.04.01910.1016/j.forsciint.2019.04.019 ↗
26. 10.1021/jm00256a00310.1021/jm00256a003 ↗
27. 10.1007/s11419-007-0039-110.1007/s11419-007-0039-1 ↗
28. European Monitoring Centre for Drugs and Drug Addiction Report on the Risk Assessment of N-PhenylN-[1-(2-Phenylethyl)piperidin-4-Yl] Furan-2-Carboxamide (Furanylfentanyl) in the Framework of the Council Decision on New Psychoactive Substances; Risk Assessments; Publications Office of the European Union: Luxembourg, 2017.
29. Huang, B.S.; Terrell, R. C.; Deutsche, K. H.; Kudzma, L. V.; Lalinde, N. L. N-aryl-N-(4-piperidinyl) amides and pharmaceutical compositions and method employing such compounds. U.S. Patent 4,584,303 A, 1986.
30. Henderson G. L. · J. Pharmacol. Exp. Ther. · 1975 · 192 · 489
31. 10.1002/anie.20151165410.1002/anie.201511654 ↗
32. 10.1124/pr.117.01390410.1124/pr.117.013904 ↗
33. 10.1021/jacs.9b0487210.1021/jacs.9b04872 ↗
34. 10.1039/D0CC02107E10.1039/D0CC02107E ↗
35. 10.1021/jacs.0c0521910.1021/jacs.0c05219 ↗
36. 10.1021/acschembio.1c0002610.1021/acschembio.1c00026 ↗
37. 10.1124/jpet.118.25367410.1124/jpet.118.253674 ↗
38. 10.1038/s41541-021-00329-010.1038/s41541-021-00329-0 ↗
39. 10.1080/21645515.2022.212250710.1080/21645515.2022.2122507 ↗
40. 10.1016/j.neuropharm.2019.10773010.1016/j.neuropharm.2019.107730 ↗
41. 10.1021/acs.jmedchem.0c0104210.1021/acs.jmedchem.0c01042 ↗
42. 10.1016/j.drugalcdep.2020.10834810.1016/j.drugalcdep.2020.108348 ↗
43. 10.1038/nri286810.1038/nri2868 ↗
44. 10.1016/s0140-6736(09)61248-410.1016/s0140-6736(09)61248-4 ↗
45. 10.1016/s1473-3099(20)30873-210.1016/s1473-3099(20)30873-2 ↗
46. 10.1093/infdis/jiaa66810.1093/infdis/jiaa668 ↗
47. 10.1159/00005003710.1159/000050037 ↗
48. 10.1016/S0264-410X(02)00266-910.1016/S0264-410X(02)00266-9 ↗
49. 10.1586/14760584.6.3.38110.1586/14760584.6.3.381 ↗
50. 10.1002/eji.20052628510.1002/eji.200526285 ↗
51. 10.1016/j.intimp.2015.09.01210.1016/j.intimp.2015.09.012 ↗
52. 10.1371/journal.pone.000254710.1371/journal.pone.0002547 ↗
53. See also U.S. Department of Justice. Lists of Scheduling Actions, Controlled Substances, Regulated Chemicals, www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf (accessed Dec 21, 2024).
54. 10.1016/j.bmcl.2007.05.03210.1016/j.bmcl.2007.05.032 ↗
55. 10.1016/j.str.2022.11.00810.1016/j.str.2022.11.008 ↗
56. 10.1006/viro.2000.037310.1006/viro.2000.0373 ↗
57. 10.1186/1477-3155-5-1010.1186/1477-3155-5-10 ↗
58. 10.1021/acsnano.8b0968310.1021/acsnano.8b09683 ↗
59. 10.1172/jci9119210.1172/jci91192 ↗
60. 10.1016/j.carres.2017.10.00610.1016/j.carres.2017.10.006 ↗
61. 10.1021/jm990370210.1021/jm9903702 ↗
62. 10.1016/j.yrtph.2010.12.00710.1016/j.yrtph.2010.12.007 ↗
63. 10.1016/j.coi.2019.03.00410.1016/j.coi.2019.03.004 ↗
64. 10.1111/j.1521-0391.2013.00314.x10.1111/j.1521-0391.2013.00314.x ↗
65. 10.1038/icb.2016.6510.1038/icb.2016.65 ↗
66. 10.1016/S0065-2776(08)60536-210.1016/S0065-2776(08)60536-2 ↗
67. aU.S. Drug Enforcement Administration. 2020 National Drug Threat Assessment, 2020. https://www.dea.gov/documents/2021/03/02/2020-national-drug-threat-assessment.
68. bDrug Enforcement Administration. National Drug Threat Assessment 2024, 2024. https://www.dea.gov/documents/2024/2024-05/2024-05-24/national-drug-threat-assessment-2024.
69. cNPS Discovery. Center for Forensic Science Research & Education Trend Reports, https://www.npsdiscovery.org/reports/trend-reports/(all accessed Dec 21, 2024), 2024.
70. 10.1080/19420862.2021.199155210.1080/19420862.2021.1991552 ↗
71. 10.1002/eji.183009081010.1002/eji.1830090810 ↗
72. 10.1186/s12896-015-0217-x10.1186/s12896-015-0217-x ↗
73. 10.1021/acs.jmedchem.1c0196710.1021/acs.jmedchem.1c01967 ↗
74. 10.1124/jpet.120.00012410.1124/jpet.120.000124 ↗
75. 10.1016/j.toxlet.2024.03.00810.1016/j.toxlet.2024.03.008 ↗