Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12.
ACS Comb Sci
; 22(3): 156-164, 2020 03 09.
Article
em En
| MEDLINE
| ID: mdl-32027120
ABSTRACT
On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Técnicas de Química Combinatória
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Proteína 1A de Ligação a Tacrolimo
Limite:
Humans
Idioma:
En
Revista:
ACS Comb Sci
Ano de publicação:
2020
Tipo de documento:
Article