Journal article
Peptide ligands of Regulators of G‐Protein Signaling 4 (RGS4) identified by screening of a focused one‐bead, one‐compound peptide library
The FASEB journal, Vol.21(6), pp.A1002-A1002
2007
DOI: 10.1096/fasebj.21.6.A1002-a
Abstract
The objective of this study is to identify peptide inhibitors of Regulator of G‐Protein Signaling 4 (RGS4) that are more potent than our lead compound, YJ34 (Ac‐Val‐Lys‐[Cys‐Thr‐Gly‐Ile‐Cys]‐Glu‐NH2, S‐S). YJ34 was rationally designed to inhibit RGS activity by mimicking the switch 1 region of Gαi based on the RGS4‐Gαi crystal structure. We used a focused One‐Bead, One‐Compound peptide library which retains structures known to be necessary for YJ34 activity. The library with 2.5 million peptides was screened and peptide‐beads with increased binding to a fluorescently labelled RGS4ΔN were isolated. The hit sequences identified can be put into a few structural groups, which may represent discrete modes of binding to RGS4. In addition, some peptides inhibit and some peptides increase RGS4ΔN binding to Gαo in a Flow Cytometery Protein Interaction Assay. One peptide decreases the intrinsic fluorescence of RGS4ΔN with a 50 nM Kd. In conclusion, we have identified peptides that have different functions and possibly different modes of binding RGS4ΔN. Functional activities of the binding peptides are currently being evaluated. Future directions include determining if peptides of similar structures can compete for binding to RGS4.
Supported by R01DA003910 to HIM, RRN.
Details
- Title: Subtitle
- Peptide ligands of Regulators of G‐Protein Signaling 4 (RGS4) identified by screening of a focused one‐bead, one‐compound peptide library
- Creators
- Rebecca A Roof - University of MichiganDavid L Roman - University of MichiganAnjanette Turbiak - University of MichiganHenry I Mosberg - University of MichiganRichard R Neubig - University of Michigan
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1002-A1002
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1002-a
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- RRN (R01DA003910) HIM (R01DA003910)
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Pharmacy; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984072090502771
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