Proven in vitro evolution of protease cathepsin E-inhibitors and -activators at pH 4.5 using a paired peptide method.
J Pept Sci
; 18(12): 711-9, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23109368
ABSTRACT
Improving a particular function of molecules is often more difficult than identifying such molecules ab initio. Here, a method to acquire higher affinity and/or more functional peptides was developed as a progressive library selection method. The primary library selection products were utilized to build a secondary library composed of blocks of 4 amino acids, of which selection led to peptides with increased activity. These peptides were further converted to randomly generate paired peptides. Cathepsin E-inhibitors thus obtained exhibited the highest activities and affinities (pM order). This was also the case with cathepsin E-activating peptides, proving the methodological effectiveness. The primary, secondary, and tertiary library selections can be regarded as module-finding, module-shuffling, and module-pairing, respectively, which resembles the progression of the natural evolution of proteins. The mode of peptide binding to their target proteins is discussed in analogy to antibodies and epitopes of an antigen.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Catepsina E
/
Aptâmeros de Peptídeos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article