Peptide biosensors for anticancer drugs: Design in silico to work in denaturizing environment

F. Guida, A. Battisti, I. Gladich, M. Buzzo, E. Marangon, L. Giodini, G. Toffoli, A. Laio, F. Berti

Research output: Contribution to journalArticlepeer-review

Abstract

One of the main targets in current clinical oncology is the development of a cheap device capable of monitoring in real-time the concentration of a drug in the blood of a patient. This would allow fine-tuning the dosage according to the patient's metabolism, a key condition to reduce side effects. By using surface plasmon resonance and fluorescence spectroscopy we here show that short peptides designed in silico by a recently developed algorithm are capable of binding the anticancer drug irinotecan (CPT-11) with micromolar affinity. Importantly, the recognition takes place in the denaturating solution used in standard therapeutic drug monitoring to detach the drug from the proteins that are present in human plasma, and some of the peptides are capable of distinguishing CPT-11 from its metabolite SN-38. These results suggest that the in silico design of small artificial peptides is now a viable route for designing sensing units, opening a wide range of applications in diagnostic and clinical areas. © 2017 Elsevier B.V.
Original languageEnglish
Pages (from-to)298-303
Number of pages6
JournalBiosensors and Bioelectronics
Volume100
DOIs
Publication statusPublished - 2018

Keywords

  • Drug monitoring
  • In silico design
  • Irinotecan
  • Peptides
  • Bioinformatics
  • Drug interactions
  • Drug products
  • Fluorescence spectroscopy
  • Patient monitoring
  • Proteins
  • Surface plasmon resonance
  • Anticancer drug
  • Artificial peptides
  • Clinical oncology
  • Human plasmas
  • In-silico
  • Therapeutic drug monitoring
  • antineoplastic agent
  • firtecan
  • irinotecan
  • methanol
  • organic solvent
  • peptide
  • algorithm
  • amino acid sequence
  • Article
  • binding affinity
  • biosensor
  • computer model
  • controlled study
  • drug blood level
  • drug monitoring
  • enzyme denaturation
  • fluorescence spectroscopy
  • metabolite
  • pH
  • protein denaturation
  • protein targeting
  • surface plasmon resonance

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