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Selection of peptides that bind to plasminogen activator inhibitor 1 (PAI‐1) using random peptide phage‐display libraries
Author(s) -
Gårdsvoll Henrik,
van Zonneveld Anton-Jan,
Holm Arne,
Eldering Eric,
van Meijer Marja,
Danø Keld,
Pannekoek Hans
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00742-x
Subject(s) - peptide library , phage display , peptide , peptide sequence , plasminogen activator , chemistry , biopanning , phagemid , serine protease , amino acid , biochemistry , microbiology and biotechnology , concatemer , biology , protease , bacteriophage , enzyme , gene , escherichia coli , genome , endocrinology
Large random hexa‐ and decapenta‐peptide libraries were constructed and displayed on the surface of the filamentous phagemid pComb8. Panning of the hexa‐peptide library on immobilized plasminogen activator inhibitor 1 (PAI‐1) specifically selected a minor fraction of concatemers, indicating that binding to PAI‐1 requires an extended amino acid sequence. Accordingly, the decapenta‐peptide library exclusively yielded PAI‐1 binding peptides of 15 amino acid residues. None of these phage‐bound peptides prevented the interaction between PAI‐1 and its target serine protease urokinase (u‐PA). To isolate peptides that block the interaction between PAI‐1 and u‐PA, phages bound to immobilized PAI‐1 were eluted by incubation with u‐PA. Remarkably, this procedure resulted in elution of a unique phage type that harbors a concatemer of decapentamers, consisting of 49 amino acid residues with no obvious similarity to the primary sequence of PAI‐1 or u‐PA.