Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction

[Image: see text] Calcineurin inhibitors such as cyclosporine A and FK506 are effective immunosuppressants but produce severe side effects. Rational modification of a previously reported peptide inhibitor, GPHPVIVITGPHEE (K(D) ∼ 500 nM), by replacing the two valine residues with tert-leucine and the...

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Autores principales: Qian, Ziqing, Dougherty, Patrick G., Liu, Tao, Oottikkal, Shameema, Hogan, Patrick G., Hadad, Christopher M., Pei, Dehua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174996/
https://www.ncbi.nlm.nih.gov/pubmed/25162754
http://dx.doi.org/10.1021/jm500743t
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author Qian, Ziqing
Dougherty, Patrick G.
Liu, Tao
Oottikkal, Shameema
Hogan, Patrick G.
Hadad, Christopher M.
Pei, Dehua
author_facet Qian, Ziqing
Dougherty, Patrick G.
Liu, Tao
Oottikkal, Shameema
Hogan, Patrick G.
Hadad, Christopher M.
Pei, Dehua
author_sort Qian, Ziqing
collection PubMed
description [Image: see text] Calcineurin inhibitors such as cyclosporine A and FK506 are effective immunosuppressants but produce severe side effects. Rational modification of a previously reported peptide inhibitor, GPHPVIVITGPHEE (K(D) ∼ 500 nM), by replacing the two valine residues with tert-leucine and the C-terminal proline with a cis-proline analogue, gave an improved inhibitor ZIZIT-cisPro, which binds to calcineurin with a K(D) value of 2.6 nM and is more resistant to proteolysis.
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spelling pubmed-41749962015-08-27 Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction Qian, Ziqing Dougherty, Patrick G. Liu, Tao Oottikkal, Shameema Hogan, Patrick G. Hadad, Christopher M. Pei, Dehua J Med Chem [Image: see text] Calcineurin inhibitors such as cyclosporine A and FK506 are effective immunosuppressants but produce severe side effects. Rational modification of a previously reported peptide inhibitor, GPHPVIVITGPHEE (K(D) ∼ 500 nM), by replacing the two valine residues with tert-leucine and the C-terminal proline with a cis-proline analogue, gave an improved inhibitor ZIZIT-cisPro, which binds to calcineurin with a K(D) value of 2.6 nM and is more resistant to proteolysis. American Chemical Society 2014-08-27 2014-09-25 /pmc/articles/PMC4174996/ /pubmed/25162754 http://dx.doi.org/10.1021/jm500743t Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Qian, Ziqing
Dougherty, Patrick G.
Liu, Tao
Oottikkal, Shameema
Hogan, Patrick G.
Hadad, Christopher M.
Pei, Dehua
Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title_full Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title_fullStr Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title_full_unstemmed Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title_short Structure-Based Optimization of a Peptidyl Inhibitor against Calcineurin-Nuclear Factor of Activated T Cell (NFAT) Interaction
title_sort structure-based optimization of a peptidyl inhibitor against calcineurin-nuclear factor of activated t cell (nfat) interaction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174996/
https://www.ncbi.nlm.nih.gov/pubmed/25162754
http://dx.doi.org/10.1021/jm500743t
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