US2008058261A1PendingUtilityA1

Protease susceptibility II

Assignee: UNIV SYDNEYPriority: Jul 17, 1998Filed: May 8, 2007Published: Mar 6, 2008

Est. expiryJul 17, 2018(expired)· nominal 20-yr term from priority

Inventors:Anthony Steven Weiss

A61P 43/00C07K 7/02A61K 38/00C07K 14/78

PatentIndex Score

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References

Claims

Abstract

The manipulation of the amino acid sequence of tropoelastin, particularly human tropoelastin, to modify its protease susceptibility is described. The modified tropoelastins include tropoelastin derivatives having modified protease susceptibility, peptidomimetic molecules which contain amino acid sequences which correspond to or incorporate the protease susceptible sequences of tropoelastin. Uses of these tropoelastin derivatives and peptidomimetic molecules are provided. Also provided are nucleic acid molecules and genetic constructs encoding the amino acid sequences of the derivatives and peptidomimetic molecules of the invention.

Claims

exact text as granted — not AI-modified

1 - 44 . (canceled)  
     
     
         45 . A peptidomimetic molecule comprising an amino acid sequence selected from the group consisting of KAPGVGGAF (SEQ ID NO:8), RAAAGLG (SEQ ID NO:9), RSLSPELREGD (SEQ ID NO:10), KAAQFGLVPGV (SEQ ID NO:11), KSAAKVAAKAQLRAA (aa 503-517 of SEQ ID NO:4), RSLSPELRE (aa 1-9 of SEQ ID NO:10) and LAAAKAAKYGAA (aa 2-13 of SEQ ID NO:13), or a part thereof which inhibits proteolysis of tropoelastin.  
     
     
         46 . The peptidomimetic molecule of  claim 45 , which has the sequence H-Ala-Ala-Lys-Ala-Gln-Leu-Arg-Ala-Ala-Ala-Gly-Leu-Gly-Ala-OH (aa 509-522 of SEQ ID NO:4) or H-Ala-Ala-Lys-Ala-Gln-Leu-Arg-R-Ala-Ala-Ala-Gly-Leu-Gly-Ala-OH (SEQ ID NO:83 (where R=a reduced peptide bond).  
     
     
         47 . The peptidomimetic molecule of  claim 45 , which is a retro-inverso pseudo peptide which has the sequence: H-D-Ala-Gly-D-Leu-Gly-D-Ala-D-Ala-D-Ala-(R)-D-Arg-D-Leu-D-Gln-D-Ala-D-Lys-D-Ala-D-Ala-OH (SEQ ID NO:84) (where R=a reduced peptide bond) or H-D-Ala-Gly-D-Leu-Gly-D-Ala-D-Ala-D-Ala-D-Arg-D-Arg-D-Leu-D-Gln-D-Ala-D-Lys-D-Ala-D-Ala-OH (SEQ ID NO:85).  
     
     
         48 . The peptidomimetic molecule of  claim 45 , which has the sequence H-Val-Pro-Gly-Ala-Leu-Ala-Ala-Ala-OH or H-Val-Pro-Gly-Ala-(R)-Leu-Ala-Ala-Ala-OH (where R=a reduced peptide bond) (aa 557-564 of SEQ ID NO:5).  
     
     
         49 . The peptidomimetic molecule of  claim 45 , which is a retro-inverso pseudo peptide which has the sequence H-D-Ala-D-Ala-D-Ala-D-Leu-(R)-D-Ala-Gly-D-Pro-D-Val-OH (where R=a reduced peptide bond) (SEQ ID NO:87) or H-D-Ala-D-Ala-D-Ala-D-Leu-D-Ala-Gly-D-Pro-D-Val-OH (SEQ ID NO:88).  
     
     
         50 . The peptidomimetic molecule of  claim 45 , which further comprises one or more attached reactive groups.  
     
     
         51 . A method for enhancing the purification of a tropoelastin comprising including a peptidomimetic molecule according to  claim 45  in a tropoelastin preparation which is being subjected to purification.  
     
     
         52 . A pharmaceutical composition comprising a peptidomimetic molecule according to  claim 45  and a pharmaceutically acceptable carrier.  
     
     
         53 . The pharmaceutical composition according to  claim 52 , which is formulated as an inhalant, emulsion, injectable or topical, composition.  
     
     
         54 . A method of reducing tissue damage related to elastolytic protease attack on elastin, comprising administering the peptidomimetic molecule of  claim 45 .  
     
     
         55 . The method according to  claim 54 , wherein the tissue is skin.  
     
     
         56 . The method according to  claim 54 , wherein the tissue is lung.  
     
     
         57 . A method of inhibiting or controlling local growth and metastases of cancer, comprising administering the peptidomimetic molecule of  claim 45 .  
     
     
         58 . A method of inhibiting cellular proliferation or growth, comprising administering the peptidomimetic molecule of  claim 45 .  
     
     
         59 . The method according to  claim 58 , wherein the proliferation or growth of smooth muscle cells, epithelial cells, endothelial cells, fibroblasts, osteocytes, chondrocytes or platelets is inhibited.  
     
     
         60 . A method of promoting wound healing, comprising administering the peptidomimetic molecule of  claim 45 .  
     
     
         61 . A cosmetic formulation for use as an anti-wrinkle or hand lotion, comprising a peptidomimetic molecule according to  claim 45  and a cosmetically acceptable carrier.  
     
     
         62 . The peptidomimetic molecule of  claim 45 , wherein the amino acid sequence selected from the group consisting of KAPGVGGAF (SEQ ID NO:8), RAAAGLG (SEQ ID NO:9), RSLSPELREGD (SEQ ID NO:10), KAAQFGLVPGV (SEQ ID NO:11), KSAAKVAAKAQLRAA (aa 503-517 of SEQ ID NO:4), RSLSPELRE (aa 1-9 of SEQ ID NO:10) and LAAAKAAKYGAA (aa 2-13 of SEQ ID NO:13), or a part thereof which inhibits proteolysis of tropoelastin, is a peptide.  
     
     
         63 . A peptidomimetic molecule comprising all or part of a peptide selected from the group consisting of KAPGVGGAF (SEQ ID NO:8), RAAAGLG (SEQ ID NO:9), RSLSPELREGD (SEQ ID NO:10), KAAQFGLVPGV (SEQ ID NO:11), KSAAKVAAKAQLRAA (aa 503-517 of SEQ ID NO:4), RSLSPELRE (aa 1-9 of SEQ ID NO:10) and LAAAKAAKYGAA (aa 2-13 of SEQ ID NO:13), or a part thereof which inhibits proteolysis of tropoelastin.  
     
     
         64 . A peptidomimetic molecule which has the sequence H-Ala-Ala-Lys-Ala-Gln-Leu-Arg-Ala-Ala-Ala-Gly-Leu-Gly-Ala-OH (aa 509-522 of SEQ ID NO:4) or H-Ala-Ala-Lys-Ala-Gln-Leu-Arg-R-Ala-Ala-Ala-Gly-Leu-Gly-Ala-OH (SEQ ID NO:83) (where R=a reduced peptide bond).  
     
     
         65 . A peptidomimetic molecule which is a retro-inverso pseudo peptide which has the sequence: H-D-Ala-Gly-D-Leu-Gly-D-Ala-D-Ala-D-Ala-(R)-D-Arg-D-Leu-D-Gln-D-Ala-D-Lys-D-Ala-D-Ala-OH (SEQ ID NO:84) (where R=a reduced peptide bond) or H-D-Ala-Gly-D-Leu-Gly-D-Ala-D-Ala-D-Ala-D-Arg-D-Arg-D-Leu-D-Gln-D-Ala-D-Lys-D-Ala-D-Ala-OH (SEQ ID NO:85).  
     
     
         66 . A peptidomimetic molecule which has the sequence H-Val-Pro-Gly-Ala-Leu-Ala-Ala-Ala-OH or H-Val-Pro-Gly-Ala-(R)-Leu-Ala-Ala-Ala-OH (where R=a reduced peptide bond) (aa 557-564 of SEQ ID NO:5).  
     
     
         67 . A peptidomimetic molecule which is a retro-inverso pseudo peptide which has the sequence H-D-Ala-D-Ala-D-Ala-D-Leu-(R)-D-Ala-Gly-D-Pro-D-Val-OH (where R=a reduced peptide bond) (SEQ ID NO:87) or H-D-Ala-D-Ala-D-Ala-D-Leu-D-Ala-Gly-D-Pro-D-Val-OH (SEQ ID NO:88).

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