Synthesis of skeletally diverse β-lactam haptens for the in vitro diagnosis of IgE-mediated drug allergy.

Autor: Peña-Mendizabal E; IDM, Universitat Politècnica de València-Universitat de València, Camino de vera s/n, 46022 Valencia, Spain. smorais@upv.es., Hua BK; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, 02138, USA.; Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, Massachusetts, 02142, USA., Ibañez-Echevarria E; Hospital Universitari i Politènic La Fe, Servicio de Alergia, Avinguda de Fernando Abril Martorell, 106, 46026 València, Spain., de Rojas DH; Allergy Therapeutics Ibérica, Avda Barcelona, 115, Edificio Brasol, 2a planta, 08970 Sant Joan Despí, Barcelona, Spain., Maquieira Á; IDM, Universitat Politècnica de València-Universitat de València, Camino de vera s/n, 46022 Valencia, Spain. smorais@upv.es.; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022, Valencia, Spain.; Unidad Mixta UPV-La Fe, Nanomedicine and Sensors, IIS La Fe, Valencia, Spain., Schreiber SL; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, 02138, USA.; Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, Massachusetts, 02142, USA., Morais S; IDM, Universitat Politècnica de València-Universitat de València, Camino de vera s/n, 46022 Valencia, Spain. smorais@upv.es.; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022, Valencia, Spain.; Unidad Mixta UPV-La Fe, Nanomedicine and Sensors, IIS La Fe, Valencia, Spain.
Jazyk: angličtina
Zdroj: Chemical communications (Cambridge, England) [Chem Commun (Camb)] 2022 May 17; Vol. 58 (40), pp. 5964-5967. Date of Electronic Publication: 2022 May 17.
DOI: 10.1039/d2cc01677j
Abstrakt: We present the first synthesis of β-lactam-derived haptens, leveraging the principles of diversity-oriented synthesis to discover compounds for drug allergy in vitro testing. We designed, synthesised, and performed in vitro immunological evaluation on 18 structurally diverse haptens derived from β-lactam antibiotics. The antigens obtained with the synthesised haptens allow for the detection of specific anti-β-lactam immunoglobulins G and E. Excellent diagnostic sensitivity (83%) and specificity (100%) were achieved when the panel of antigens was tested against a cohort of 31 human serum samples using a multiplexed compact disc-based in vitro testing tool. We posit that adopting this strategy could aid β-lactam delabeling initiatives.
Databáze: MEDLINE