Document Detail


Isolation of erythropoietin receptor agonist peptides using evolved phage libraries.
MedLine Citation:
PMID:  9820589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclic peptides capable of activating the erythropoietin receptor (EPOR) were isolated from phage display libraries by screening with a novel EPOR-IgG fusion protein reagent. A parental clone ERB1 (EPO Receptor Binder 1) was first isolated from a phage display library displaying 38 random amino acids as an N-terminal fusion with the M13 minor capsid protein, pill. An evolved library was then produced from the parental sequence using an oligonucleotide saturation mutagenesis strategy which yielded EPOR binding sequences with 20 times the relative affinity of ERB1. Two synthetic peptides were constructed from these sequences both of which bind the EPO receptor in specific ELISA, and act as full agonists in EPO dependent cell proliferation assays. These peptides are 18 amino acids in length, disulfide-bonded, and have a minimum consensus sequence of CXXGWVGXCXXW, where X represents positions tolerant of several amino acids.
Authors:
S J McConnell; T Dinh; M H Le; S J Brown; K Becherer; K Blumeyer; C Kautzer; F Axelrod; D G Spinella
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological chemistry     Volume:  379     ISSN:  1431-6730     ISO Abbreviation:  Biol. Chem.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-01-08     Completed Date:  1999-01-08     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1279-86     Citation Subset:  IM    
Affiliation:
Biological Screening Group, Chugai Biopharmaceuticals, Inc., San Diego, CA 92121, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Bacteriophage M13 / genetics*
Base Sequence
COS Cells
Cloning, Molecular
Erythropoietin / chemistry,  metabolism
Humans
Molecular Mimicry
Molecular Sequence Data
Peptides / genetics,  isolation & purification*,  metabolism
Protein Binding
Receptors, Erythropoietin / agonists*,  metabolism
Sequence Homology, Amino Acid
Chemical
Reg. No./Substance:
0/Peptides; 0/Receptors, Erythropoietin; 11096-26-7/Erythropoietin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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