Stabilized bioactive peptides and methods of identification,...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/72 (2006.01) A61K 35/76 (2006.01) A61K 38/00 (2006.01) C07H 21/00 (2006.01) C07H 21/04 (2006.01) C07K 1/00 (2006.01) C07K 1/107 (2006.01) C07K 7/06 (2006.01) C07K 7/08 (2006.01) C07K 14/585 (2006.01) C07K 14/59 (2006.01) C07K 14/605 (2006.01) C07K 14/61 (2006.01) C07K 14/62 (2006.01) C07K 14/645 (2006.01) C12N 15/00 (2006.01) C12N 15/16 (2006.01) C12N 15/17 (2006.01) C12N 15/18 (2006.01) C12N 15/63 (2006.01) C12N 15/70 (2006.01) C12P 21/02 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2493306

An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an .alpha.-helical moiety, or one or more proline residues.

Un système de sélection intracellulaire permet de cribler la bioactivité et la stabilité des peptides. Des peptides recombinés aléatoires sont criblés pour leur bioactivité dans un système d'expression bien régulé, de préférence des dérivés d'une opéron lac de type sauvage. Les peptides bioactifs ainsi identifiés sont résistants de manière inhérente à la protéase et à la peptidase. L'invention concerne également des peptides bioactifs stabilisés par un groupe stabilisateur sur le N terminal, le C terminal ou les deux à la fois. Le groupe de stabilisation peut être une petite protéine stable, telle que la protéine Rop, la sulfotrasnférase de glutathione, la thiorédoxine, la protéine de liaison de la maltose, ou la réductase de glutathione, une fraction .alpha.-hélicoidale, ou un ou plusieurs résidus de proline.

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