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Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase.

Publication ,  Journal Article
Mukherjee, RP; Yow, G-Y; Sarakbi, S; Menegatti, S; Gurgel, PV; Carbonell, RG; Bobay, BG
Published in: Comput Biol Chem
February 2023

Butyrylcholinesterase (BChE) is recognized as a high value biotherapeutic in the treatment of Alzheimer's disease and drug addiction. This study presents the rational design and screening of an in-silico library of trimeric peptides against BChE and the experimental characterization of peptide ligands for purification. The selected peptides consistently afforded high BChE recovery (> 90 %) and purity, yielding up to a 1000-fold purification factor. This study revealed a marked anti-correlated conformational movement governed by the ionic strength and pH of the aqueous environment, which ultimately controls BChE binding and release during chromatographic purification; and highlighted the role of residues within and allosteric to the catalytic triad of BChE in determining biorecognition, thus providing useful guidance for ligand design and affinity maturation.

Duke Scholars

Published In

Comput Biol Chem

DOI

EISSN

1476-928X

Publication Date

February 2023

Volume

102

Start / End Page

107797

Location

England

Related Subject Headings

  • Peptides
  • Molecular Docking Simulation
  • Ligands
  • Cholinesterase Inhibitors
  • Butyrylcholinesterase
  • Bioinformatics
  • 46 Information and computing sciences
  • 34 Chemical sciences
  • 31 Biological sciences
  • 08 Information and Computing Sciences
 

Citation

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Mukherjee, R. P., Yow, G.-Y., Sarakbi, S., Menegatti, S., Gurgel, P. V., Carbonell, R. G., & Bobay, B. G. (2023). Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase. Comput Biol Chem, 102, 107797. https://doi.org/10.1016/j.compbiolchem.2022.107797
Mukherjee, Rudra Palash, Geok-Yong Yow, Samuel Sarakbi, Stefano Menegatti, Patrick V. Gurgel, Ruben G. Carbonell, and Benjamin G. Bobay. “Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase.Comput Biol Chem 102 (February 2023): 107797. https://doi.org/10.1016/j.compbiolchem.2022.107797.
Mukherjee RP, Yow G-Y, Sarakbi S, Menegatti S, Gurgel PV, Carbonell RG, et al. Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase. Comput Biol Chem. 2023 Feb;102:107797.
Mukherjee, Rudra Palash, et al. “Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase.Comput Biol Chem, vol. 102, Feb. 2023, p. 107797. Pubmed, doi:10.1016/j.compbiolchem.2022.107797.
Mukherjee RP, Yow G-Y, Sarakbi S, Menegatti S, Gurgel PV, Carbonell RG, Bobay BG. Integrated in silico and experimental discovery of trimeric peptide ligands targeting Butyrylcholinesterase. Comput Biol Chem. 2023 Feb;102:107797.
Journal cover image

Published In

Comput Biol Chem

DOI

EISSN

1476-928X

Publication Date

February 2023

Volume

102

Start / End Page

107797

Location

England

Related Subject Headings

  • Peptides
  • Molecular Docking Simulation
  • Ligands
  • Cholinesterase Inhibitors
  • Butyrylcholinesterase
  • Bioinformatics
  • 46 Information and computing sciences
  • 34 Chemical sciences
  • 31 Biological sciences
  • 08 Information and Computing Sciences