Abstract:
: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 1.2x10(7)) on 90-microm 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 microM.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Liu T,Joo SH,Voorhees JL,Brooks CL,Pei Ddoi
10.1016/j.bmc.2008.01.015subject
Has Abstractpub_date
2009-02-01 00:00:00pages
1026-33issue
3eissn
0968-0896issn
1464-3391pii
S0968-0896(08)00017-5journal_volume
17pub_type
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