Conformationally-restricted combinatorial library...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 2/00 (2006.01) C07K 1/04 (2006.01) C07K 4/00 (2006.01) C07K 14/00 (2006.01) C12Q 1/25 (2006.01) G01N 33/53 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2224086

Combinatorial libraries of different-sequence peptide members is disclosed. The libraries are comprised of stabilized, alpha-helical polypeptides having a similar tertiary structure but different amino acid residues at specific, "variable" positions in the sequence. The polypeptides are stabilized through coiled-coil interactions with other .alpha.-helical polypeptides and/or via intrahelical lactam bridges. Also disclosed are methods for using such libraries to screen for selected macromolecular ligands.

L'invention se rapporte à des banques combinatoires dont les membres sont des peptides ayant des séquences différentes. Les banques comprennent des polypeptides en hélice alpha stabilisés dotés d'une structure tertiaire similaire mais comportant des restes d'acides aminés différents qui ont des positions spécifiques "variables" dans la séquence. Les polypeptides sont stabilisés par des interactions de type bitorsadé avec d'autres polypeptides en hélice alpha et/ou via des ponts de lactame intra-hélice. On décrit par ailleurs des procédés applicables à l'utilisation de telles banques pour le criblage de ligands macromoléculaires spécifiques.

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