کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1360605 | 981442 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and screening of a cyclic peptide library: Discovery of small-molecule ligands against human prolactin receptor Synthesis and screening of a cyclic peptide library: Discovery of small-molecule ligands against human prolactin receptor](/preview/png/1360605.png)
Prolactin receptor is involved in normal lactation and reproduction; however, excessive prolactin levels can cause various reproductive disorders such as prolactinomas. Small-molecule antagonists against the human prolactin receptor (hPRLr) thus have potential clinical applications and may serve as useful molecular probes in biomedical research. In this work, we synthesized a large, support-bound cyclic peptide library (theoretical diversity of 1.2 × 107) on 90-μm TentaGel beads and screened it against the extracellular domain of hPRLr. To facilitate hit identification, each TentaGel bead was spatially segregated into outer and inner layers, with a cyclic peptide displayed on the bead surface while the bead interior contained the corresponding linear peptide. The identity of a positive bead was revealed by sequencing the linear encoding peptide within the bead by partial Edman degradation/mass spectrometry. Screening of the library resulted in 20 hits, two of which were selected for further analysis and shown to bind to hPRLr with dissociation constants of 2–3 μM.
A cyclic peptide library was screened against the extracellular domain of human prolactin receptor and ligands with low-micromolar dissociation constants were discovered.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 3, 1 February 2009, Pages 1026–1033