Discovery of the improved antagonistic prolactin variants by library screening
| Autor: | Jinchao Zhang, Yun Liu, Sean Hu, Jens Breinholt, Wei Guo, Leif Christensen, Tengkun Li, Jingyuan Zhang, Jingjing Mao, Wei Gong, Jianhe Chen, Svetlana Panina, Lingyun Wang, Leif Nørskov-Lauritsen, Meng Kong, Zibing Liu, Qinhong Ma |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Receptors Prolactin Mutant Breast Neoplasms Bioengineering Plasma protein binding Biology Pharmacology medicine.disease_cause Biochemistry In vivo medicine Humans Potency Receptor Molecular Biology Mutation Human Growth Hormone Prostatic Neoplasms Surface Plasmon Resonance Prolactin In vitro High-Throughput Screening Assays Female hormones hormone substitutes and hormone antagonists Protein Binding Biotechnology |
| Zdroj: | Protein Engineering Design and Selection. 24:855-860 |
| ISSN: | 1741-0134 1741-0126 |
| Popis: | Prolactin (PRL), a potent growth stimulator of the mammary epithelium, has been suggested to be a factor contributing to the development and progression of breast and prostate cancer. Several PRL receptor (PRLR) antagonists have been identified in the past decades, but their in vivo growth inhibitory potency was restricted by low receptor affinity, rendering them pharmacologically unattractive for clinical treatment. Thus, higher receptor affinity is essential for the development of improved PRLR antagonistic variants with improved in vivo potency. In this study, we generated Site 1 focused protein libraries of human G129R-PRL mutants and screened for those with increased affinity to the human PRLR. By combining the mutations with enhanced affinities for PRLR, we identified a novel G129R-PRL variant with mutations at Site 1 that render nearly 50-fold increase in the antagonistic potency in vitro. |
| Databáze: | OpenAIRE |
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