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Evaluation of polyanionic cyclodextrins as high affinity binding scaffolds for fentanyl.
Mayer, Brian P; Kennedy, Daniel J; Lau, Edmond Y; Valdez, Carlos A.
Afiliación
  • Mayer BP; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
  • Kennedy DJ; Nuclear and Chemical Sciences Division, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA, L-090 94550, USA.
  • Lau EY; Forensic Science Center, Lawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
  • Valdez CA; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
Sci Rep ; 13(1): 2680, 2023 02 15.
Article en En | MEDLINE | ID: mdl-36792632
Cyclodextrins (CDs) have been previously shown to display modest equilibrium binding affinities (Ka ~ 100-200 M-1) for the synthetic opioid analgesic fentanyl. In this work, we describe the synthesis of new CDs possessing extended thioalkylcarboxyl or thioalkylhydroxyl moieties and assess their binding affinity towards fentanyl hydrochloride. The optimal CD studied displays a remarkable affinity for the opioid of Ka = 66,500 M-1, the largest value reported for such an inclusion complex to date. One dimensional 1H Nuclear Magnetic Resonance (NMR) as well as Rotational Frame Overhauser Spectroscopy (2D-ROESY) experiments supported by molecular dynamics (MD) simulations suggest an unexpected binding behavior, with fentanyl able to bind the CD interior in one of two distinct orientations. Binding energies derived from the MD simulations work correlate strongly with NMR-derived affinities highlighting its utility as a predictive tool for CD candidate optimization. The performance of these host molecules portends their utility as platforms for medical countermeasures for opioid exposure, as biosensors, and in other forensic science applications.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ciclodextrinas Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ciclodextrinas Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido