Phage display identification of functional binding peptides against 4-acetamidophenol (Paracetamol): An exemplified approach to target low molecular weight organic molecules

Smith, Matthew W., Smith, Jonathan W., Harris, Charlotte, Allender, Christopher John, Brancale, Andrea and Gumbleton, Mark ORCID: https://orcid.org/0000-0002-7386-311X 2007. Phage display identification of functional binding peptides against 4-acetamidophenol (Paracetamol): An exemplified approach to target low molecular weight organic molecules. Biochemical and Biophysical Research Communications 358 (1) , pp. 285-291. 10.1016/j.bbrc.2007.04.122

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Abstract

Peptide-phage display has been widely used to explore protein–protein interactions, however, despite the potential range of applications the use of this technology to identify peptides that bind low molecular weight organic molecules has not been explored. In this current study, we identified a phage clone (PARA-061) displaying the cyclic 7-mer peptide sequence N?AC-NPNNLSH-CGGGSC? that binds the low molecular weight organic molecule 4-acetamidophenol (4-AAP; paracetamol). To avoid occupancy of key functional groups on the target 4-AAP molecule our panning strategy was directed against insoluble complexes of 4-AAP rather than against the target linked to a stationary support or bearing an affinity tag. To augment the panning procedure we deleted phage that also bound the 4-AAP isomers, 2-AAP and 3-AAP. The identified PARA-061 peptide-phage clone displayed functional binding properties against 4-AAP in solution, able in a peptide sequence-dependant manner to prevent the in vitro hepatotoxicity of 4-AAP and reduce (not, vert, similar20%) the permeability of 4-AAP across a semi-permeable membrane. Molecular dynamic simulations generated a stable binding conformation between the PARA-061 peptide sequence and 4-AAP. In conclusion, we show that a phage display library can be used to identify peptide sequence-specific clones able to modulate the functional binding of a low molecular weight organic molecule. Such peptides may be expected to find utility in the next generation of hybrid polymer-based biosensing devices.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Uncontrolled Keywords:	Phage display; Peptide; 4-Acetamidophenol; Paracetamol; Low molecular weight organic molecules; Insoluble complexes
Publisher:	Elsevier
ISSN:	0006-291X
Last Modified:	26 Jun 2024 15:15
URI:	https://orca.cardiff.ac.uk/id/eprint/959

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