Premium
Identification of chymotrypsin inhibitors from a second‐generation template assisted combinatorial peptide library
Author(s) -
Mcbride Jeffrey D.,
Freeman Hamzah N.,
Leatherbarrow Robin J.
Publication year - 2000
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/1099-1387(200009)6:9<446::aid-psc283>3.0.co;2-u
Subject(s) - combinatorial chemistry , identification (biology) , chymotrypsin , chemistry , peptide , computational biology , biochemistry , biology , enzyme , trypsin , botany
In an earlier study (McBride JD, Freeman N, Domingo GJ, Leatherbarrow RJ. Selection of chymotrypsin inhibitors from a conformationally‐constrained combinatorial peptide library. J. Mol. Biol. 1996; 259 : 819–827) we described a resin‐bound cyclic peptide library, constructed based on the sequence of the anti‐tryptic reactive site loop of Bowman–Birk Inhibitor (BBI), a proteinase inhibitor protein. This library was used to identify re‐directed chymotrypsin inhibitors with K i values as low as 17 n m . We have now extended this work by constructing an enhanced library in which a further position, at the P 4 site of the inhibitor, has been randomized. This new library has variation at three target locations ( P 4 , P 1 and P 2 ′) within the inhibitory loop region, producing 8000 variants. Screening this library allowed selection of new inhibitor sequences with K i values as low as 3.4 n m . The success of this approach is reflected by the fact that the inhibition constant given by the selected peptide sequence is slightly lower than that reported against chymotrypsin for the most studied full length BBI protein, Soybean BBI 2‐IV. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.