Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril

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Title
Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril
Author(s)
Zoheb Hirani; Hailey F. Taylor; Emily F. Babcock; Andrew T. Bockus; C. Daniel Varnado Jr; Christopher W. Bielawski; Adam R. Urbach
Publication Date
2018-09
Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.140, no.38, pp.12263 - 12269
Publisher
AMER CHEMICAL SOC
Abstract
This Article describes the molecular recognition of peptides containing an N-terminal methionine (Met) by the synthetic receptor cucurbit[8]uril (Q8) in aqueous solution and with submicromolar affinity. Prior work established that Q8 binds with high affinity to peptides containing aromatic amino acids, either by simultaneous binding of two aromatic residues, one from each of two different peptides, or by simultaneous binding of an aromatic residue and its immediate neighbor on the same peptide. The additional binding interface of two neighboring residues suggested the possibility of targeting nonaromatic peptides, which have thus far bound only weakly to synthetic receptors. A peptide library designed to test this hypothesis was synthesized and screened qualitatively for Q8 binding using a fluorescent indicator displacement assay. The large fluorescence response observed for several Met-terminated peptides suggested strong binding, which was confirmed quantitatively by the determination of submicromolar equilibrium dissociation constant values for Q8 binding to MLA, MYA, and MFA using isothermal titration calorimetry (ITC). This discovery of high affinity binding to Met-terminated peptides and, more generally, to nonaromatic peptides prompted a detailed investigation of the determinants of binding in this system using ITC, electrospray ionization mass spectrometry, and 1H NMR spectroscopy for 25 purified peptides. The studies establish the sequence determinants required for high-affinity binding of Met-terminated peptides and demonstrate that cucurbit[n]uril-mediated peptide recognition does not require an aromatic residue for high affinity. These results, combined with the known ability of cucurbit[n]urils to target N-termini and disordered loops in folded proteins, suggest that Q8 could be used to target unmodified, Met-terminated proteins. © 2018 American Chemical Society
URI
https://pr.ibs.re.kr/handle/8788114/5179
ISSN
0002-7863
Appears in Collections:
Center for Multidimensional Carbon Materials(다차원 탄소재료 연구단) > Journal Papers (저널논문)
Files in This Item:
1. jacs.8b07865.pdfDownload

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