Conformational Stabilization and Rapid Labeling of a 29-Residue Peptide by a Small Molecule Reaction Partner
Name
Manuscript - A 29-amino-acid peptide.pdf
Description
Accepted version
Size
3.38 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Evans, Ethan Daniel
Gates, Zachary P
Sun, Zhen-Yu J.
Mijalis, Alexander James
Pentelute, Bradley L.
Date Issued
February 2019
Journal
Biochemistry
Publisher
American Chemical Society (ACS)
Citation
Evans, Ethan D. et al. "Conformational Stabilization and Rapid Labeling of a 29-Residue Peptide by a Small Molecule Reaction Partner." Biochemistry 58, 10 (February 2019): 1343–1353 © 2019 American Chemical Society.
Version
Author's final manuscript
Abstract
A 29-residue peptide (MP01), identified by in vitro selection for reactivity with a small molecule perfluoroaromatic, was modified and characterized using experimental and computational techniques, with the goal of understanding the molecular basis of its reactivity. These studies identified a six-amino acid point mutant (MP01-Gen4) that exhibited a reaction rate constant of 25.8 ± 1.8 M-1 s-1 at pH 7.4 and room temperature, approximately 2 orders of magnitude greater than that of its progenitor sequence and 3 orders of magnitude greater than background cysteine reactivity. MP01-Gen4 appeared to be conformationally dynamic and exhibited several properties reminiscent of larger protein molecules, including denaturant-sensitive structure and reactivity. We believe the majority of the reaction rate enhancement can be attributed to interaction of MP01-Gen4 with the perfluoroaromatic probe, which was found to stabilize a helical conformation of both MP01-Gen4 and nonreactive Cys-to-Ser or Cys-to-Ala variants. These findings demonstrate the ability of dynamic peptides to access proteinlike reaction mechanisms and the potential of perfluoroaromatic functionality to stabilize small peptide folds.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/acs.biochem.8b00940
