Unknown

Dataset Information

0

Structure-based optimization of a peptidyl inhibitor against calcineurin-nuclear factor of activated T cell (NFAT) interaction.


ABSTRACT: 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 (KD ? 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 KD value of 2.6 nM and is more resistant to proteolysis.

SUBMITTER: Qian Z 

PROVIDER: S-EPMC4174996 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structure-based optimization of a peptidyl inhibitor against calcineurin-nuclear factor of activated T cell (NFAT) interaction.

Qian Ziqing Z   Dougherty Patrick G PG   Liu Tao T   Oottikkal Shameema S   Hogan Patrick G PG   Hadad Christopher M CM   Pei Dehua D  

Journal of medicinal chemistry 20140904 18


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 (KD ∼ 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 KD value of 2.6 nM and is more resistant to proteolysis. ...[more]

Similar Datasets

| S-EPMC8011862 | biostudies-literature
| S-EPMC3171643 | biostudies-literature
| S-EPMC2666591 | biostudies-literature
| S-EPMC7891853 | biostudies-literature
| S-EPMC4018210 | biostudies-literature
| S-EPMC7288753 | biostudies-literature
| S-EPMC3031470 | biostudies-literature
| S-EPMC3670844 | biostudies-literature
| S-EPMC5104941 | biostudies-literature
| S-EPMC3029683 | biostudies-literature