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Phage-Display-Derived Peptide Specific to Carbamylated Protein
[Image: see text] Protein carbamylation has been linked with diseases commonly associated with patients with reduced kidney function. Carbamylated human serum albumin (cHSA), which has been proven to be nephrotoxic and associated with heart failure for chronic kidney disease (CKD) patients, was chos...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860060/ https://www.ncbi.nlm.nih.gov/pubmed/33553925 http://dx.doi.org/10.1021/acsomega.0c05481 |
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author | Ma, Yuhao Wu, Meng Li, Shuhui Tonelli, Marcello Unsworth, Larry D. |
author_facet | Ma, Yuhao Wu, Meng Li, Shuhui Tonelli, Marcello Unsworth, Larry D. |
author_sort | Ma, Yuhao |
collection | PubMed |
description | [Image: see text] Protein carbamylation has been linked with diseases commonly associated with patients with reduced kidney function. Carbamylated human serum albumin (cHSA), which has been proven to be nephrotoxic and associated with heart failure for chronic kidney disease (CKD) patients, was chosen for our study. Through phage display against cHSA, one specific peptide sequence (cH2-p1) was identified with higher selectivity toward cHSA over native HSA. The cH2-p1 peptide was synthesized, and its target binding was analyzed through isothermal titration calorimetry (ITC). The result showed that cH2-p1 was able to bind cHSA of different levels of carbamylation with a similar dissociation constant of ∼1.0 × 10(–4) M. This peptide also showed a binding specificity to carbamylated fibrinogen (cFgn), while not binding to native Fgn at all. For better understanding of the binding mechanism of cH2-p1, competitive binding of cH2-p1 and anti-homocitrulline to cHSA was performed, and the result revealed that cH2-p1 may bind to homocitrulline residues in a similar manner to the antibody. A molecular docking study was further performed to investigate the favored binding conformation of homocitrulline residue to cH2-p1. This work demonstrates the potential of peptides as a specific binding element to carbamylated proteins. |
format | Online Article Text |
id | pubmed-7860060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-78600602021-02-05 Phage-Display-Derived Peptide Specific to Carbamylated Protein Ma, Yuhao Wu, Meng Li, Shuhui Tonelli, Marcello Unsworth, Larry D. ACS Omega [Image: see text] Protein carbamylation has been linked with diseases commonly associated with patients with reduced kidney function. Carbamylated human serum albumin (cHSA), which has been proven to be nephrotoxic and associated with heart failure for chronic kidney disease (CKD) patients, was chosen for our study. Through phage display against cHSA, one specific peptide sequence (cH2-p1) was identified with higher selectivity toward cHSA over native HSA. The cH2-p1 peptide was synthesized, and its target binding was analyzed through isothermal titration calorimetry (ITC). The result showed that cH2-p1 was able to bind cHSA of different levels of carbamylation with a similar dissociation constant of ∼1.0 × 10(–4) M. This peptide also showed a binding specificity to carbamylated fibrinogen (cFgn), while not binding to native Fgn at all. For better understanding of the binding mechanism of cH2-p1, competitive binding of cH2-p1 and anti-homocitrulline to cHSA was performed, and the result revealed that cH2-p1 may bind to homocitrulline residues in a similar manner to the antibody. A molecular docking study was further performed to investigate the favored binding conformation of homocitrulline residue to cH2-p1. This work demonstrates the potential of peptides as a specific binding element to carbamylated proteins. American Chemical Society 2021-01-25 /pmc/articles/PMC7860060/ /pubmed/33553925 http://dx.doi.org/10.1021/acsomega.0c05481 Text en © 2021 The Authors. Published by American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Ma, Yuhao Wu, Meng Li, Shuhui Tonelli, Marcello Unsworth, Larry D. Phage-Display-Derived Peptide Specific to Carbamylated Protein |
title | Phage-Display-Derived Peptide
Specific to Carbamylated Protein |
title_full | Phage-Display-Derived Peptide
Specific to Carbamylated Protein |
title_fullStr | Phage-Display-Derived Peptide
Specific to Carbamylated Protein |
title_full_unstemmed | Phage-Display-Derived Peptide
Specific to Carbamylated Protein |
title_short | Phage-Display-Derived Peptide
Specific to Carbamylated Protein |
title_sort | phage-display-derived peptide
specific to carbamylated protein |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860060/ https://www.ncbi.nlm.nih.gov/pubmed/33553925 http://dx.doi.org/10.1021/acsomega.0c05481 |
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