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Highly Selective Cyclic Peptide Ligands for NeutrAvidin and Avidin Identified by Phage Display
Author(s) -
Meyer Scott C.,
Gaj Thomas,
Ghosh Indraneel
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00401.x
Subject(s) - biotinylation , streptavidin , avidin , phage display , peptide , peptide library , chemistry , cyclic peptide , chemical biology , combinatorial chemistry , biotin , protein tag , biochemistry , computational biology , peptide sequence , biology , fusion protein , gene , recombinant dna
Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage‐display selections, biotinylated macromolecular targets are often immobilized on avidin‐ and streptavidin‐functionalized supports. Thus, the characterization of peptides that bind avidin and streptavidin is necessary for accurate interpretation of screening and selection results. Toward this goal, we panned a phage‐displayed cyclic peptide library against NeutrAvidin, a chemically deglycosylated version of avidin. The selection produced a highly homologous consensus motif (Asp‐Arg/Leu‐Ala‐Ser/Thr‐Pro‐Tyr/Trp). Two of these cyclic peptides, CDRATPYC and CDRASPYC, bound both NeutrAvidin and avidin with low‐micromolar dissociation constants, whereas their acyclic counterparts had negligible affinity (<80‐fold). Moreover, these cyclic peptides were very specific for their targets and did not bind the structurally and functionally similar protein, streptavidin. Thus, we have identified a new class of cyclic peptides, distinct from the much‐studied streptavidin‐binding His‐Pro‐Gln peptide motif. These results will not only allow for discriminating between desired and background cyclic peptide motifs in selections and screens but also provide a new protein/peptide model system and a useful reagent in chemical biology that can have utility in protein immobilization, purification, and chemical tagging.