Peptide Stapling: A Strategy for Enhanced Molecular Recognition of C-Reactive Protein
4 affiliations
- 1Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, Prague, Czech Republic, 166 10
- 2Faculty of Chemistry, University of Warsaw, Pasteura 1, Warsaw, Poland, 02-093
- 3Faculty of Biology, University of Gdansk, Wita Stwosza 59, Gdansk, Poland, 80-308
- 4Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, Warsaw, Poland, 01-224
Abstract
In our previous studies, we identified three linear CRP‑binding peptides (P2, P3, and P9), which were subsequently characterized using experimental approaches and in silico analysis. The P3 peptide was successfully used as a sensing element in a microfluidic sensing device for CRP recognition 1. However, linear peptides have some limitations, such as conformational instability. Thus, in our study, we constrained the peptide structure using a stapling approach (P1) to address this problem. In silico analysis showed that only the P9 peptide retained CRP-binding activity after the stapling reaction among other CRP-binding peptides reported in our previous studies 1. Calculations indicated that the staple-bound peptide P1 has a higher affinity for CRP than the linear peptide P9, which lacks a staple. Furthermore, the calculated binding energy for P1 was lower than that obtained for the stapled peptides P2 and P3. The staple in peptide P1 was formed via ring-closing olefin metathesis (RCM). Structural differences between the new stapled P1 peptide and the linear P9 peptide were demonstrated using transmission electron microscopy (TEM) and circular dichroism (CD) measurements. The stapled P1 peptide was applied to recognize CRP on silicate-modified indium tin oxide-coated glass electrodes. The electrodes obtained with P1 exhibit a greater affinity for CRP, even in the presence of proteolytic enzymes, than those modified with the linear P9 peptide. The thermal and proteolytic stability of the peptides was evaluated using electrochemical analyses and CD.
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BibTeX
@misc{lubos2026peptide,
title = {{Peptide Stapling: A Strategy for Enhanced Molecular Recognition of C-Reactive Protein}},
author = {Marta Lubos and Jan Pícha and Jakub Kaminský and Magdalena Majewska and Magdalena Narajczyk and Jiří Jiráček and Katarzyna Szot-Karpińska},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15011054/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011054/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Peptide Stapling: A Strategy for Enhanced Molecular Recognition of C-Reactive Protein
AU - Marta Lubos
AU - Jan Pícha
AU - Jakub Kaminský
AU - Magdalena Majewska
AU - Magdalena Narajczyk
AU - Jiří Jiráček
AU - Katarzyna Szot-Karpińska
PY - 2026
DA - 2026/10/26
PB - ChemRxiv
DO - 10.26434/chemrxiv.15011054/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011054/v1
AB - In our previous studies, we identified three linear CRP‑binding peptides (P2, P3, and P9), which were subsequently characterized using experimental approaches and in silico analysis. The P3 peptide was successfully used as a sensing element in a microfluidic sensing device for CRP recognition 1. However, linear peptides have some limitations, such as conformational instability. Thus, in our study, we constrained the peptide structure using a stapling approach (P1) to address this problem. In silico analysis showed that only the P9 peptide retained CRP-binding activity after the stapling reaction among other CRP-binding peptides reported in our previous studies 1. Calculations indicated that the staple-bound peptide P1 has a higher affinity for CRP than the linear peptide P9, which lacks a staple. Furthermore, the calculated binding energy for P1 was lower than that obtained for the stapled peptides P2 and P3. The staple in peptide P1 was formed via ring-closing olefin metathesis (RCM). Structural differences between the new stapled P1 peptide and the linear P9 peptide were demonstrated using transmission electron microscopy (TEM) and circular dichroism (CD) measurements. The stapled P1 peptide was applied to recognize CRP on silicate-modified indium tin oxide-coated glass electrodes. The electrodes obtained with P1 exhibit a greater affinity for CRP, even in the presence of proteolytic enzymes, than those modified with the linear P9 peptide. The thermal and proteolytic stability of the peptides was evaluated using electrochemical analyses and CD.
ER -