Cyclic peptide libraries and methods of use thereof to...

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G01N 33/68 (2006.01) C07K 1/04 (2006.01) C07K 1/14 (2006.01) C07K 4/00 (2006.01) C07K 7/64 (2006.01) C12Q 1/37 (2006.01) C12Q 1/42 (2006.01) C12Q 1/48 (2006.01)

Patent

CA 2290993

Methods for determining an optimal binding motif for a binding compound are provided in which the binding compound is contacted with an oriented degenerate cyclic peptide library (ODCPL) under conditions which allow for interaction between the binding compound and the ODCPL such that a complex is formed between the binding compound and a subpopulation of library members capable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is then separated from library members that are incapable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is linearized to form a subpopulation of linearized library members. The amino acid sequence of the subpopulation of linearized library members is determined and an amino acid sequence motif is then determined for an interaction site of the binding compound, based upon the relative abundance of different amino acid residues at each degenerate position within the linearized library members. Oriented degenerate cyclic peptide libraries, and methods for purifying cyclic peptides from linear peptides, are also provided.

Procédés pour déterminer un motif structural de liaison pour un composé de liaison. Le composé de liaison est mis en contact avec une banque de peptides cycliques dégénérés orientés (ODCPL: oriented degenerate cyclic peptide library) dans des conditions qui permettent une interaction entre le composé de liaison et l'ODCPL entraînant la formation d'un complexe entre le composé de liaison et une sous-population d'éléments de la banque capables d'interagir avec le composé de liaison . La sous-population d'éléments de la banque capables d'interagir avec le composé de liaison est ensuite séparée des éléments de la banque incapables d'interagir avec le composé de liaison. La sous-population d'éléments de la banque capable d'interagir avec le composé de liaison est linéarisée pour former une sous-population d'éléments de banque linéarisés. On détermine ensuite la séquence d'acide aminé de la sous-population d'éléments de banque linéarisés et on détermine un motif structural de séquence d'acide aminé pour un site d'interaction du composé de liaison, basé sur l'abondance relative des différents résidus d'acide aminé à chaque position dégénérée dans les éléments de banque linéarisés. L'invention décrit en outre des banques de peptides cycliques dégénérés orientés et des procédés pour purifier les peptides cycliques à partir de peptides linéaires.

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