Modifications of peptide compositions to increase stability...

A - Human Necessities – 61 – K

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A61K 38/16 (2006.01) C07K 1/107 (2006.01) C07K 7/00 (2006.01) C07K 19/00 (2006.01) C07K 14/16 (2006.01) C12N 9/12 (2006.01)

Patent

CA 2675665

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A "therapeutic peptide composition" comprises a "carrier peptide" and a "cargo peptide." A "carrier peptide" is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The "cargo peptide" is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

L'invention concerne des procédés de modification de compositions peptidiques destinés à augmenter la stabilité et l'efficacité de distribution. Spécifiquement, l'invention décrite concerne des procédés pour augmenter la stabilité et l'efficacité d'administration de compositions peptidiques modulatrices de protéine kinase C (PKC). Une <= composition peptidique thérapeutique >= comprend un<= peptide porteur >= et un <= peptide cargo >=. Un <= peptide porteur >= est un peptide ou une séquence d'acide aminé dans un peptide qui facilite l'absorption cellulaire de la composition peptidique thérapeutique. Le <= peptide cargo >= est un peptide modulateur dePKC. Des modifications peptidiques soit du peptide porteur, soit du peptide cargo, ou des deux, qui sont décrites ici augmentent la stabilité et l'efficacité d'administration de compositions peptidiques thérapeutiques en réduisant l'échange de liaison disulfure, la stabilité physique, en réduisant la dégradation protéolytique et en augmentant l'efficacité d'absorption cellulaire.

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