| 摘要 |
The invention relates to polypeptides containing a cytoplasmic domain ending with a MAST-2 binding domain, from 11 to 13 residues, the first two residues of which are S and W, and the last four residues of which are Q, T, R and L, the polypeptides presenting a high affinity for the PDZ domain of the human MAST2 protein. The invention also relates to polynucleotides, vectors, lentiviral particles, cells as well as compositions containing the same. The invention is also directed to the use of the polypeptides, polynucleotides, vectors, lentiviral particles, cells and compositions in the treatment and/or prevention of a disease, disorder or condition, which alters the Central Nervous System (CNS) and/or the Peripheral Nervous System (PNS). The invention also concerns molecular signatures of cellular genes to determine the neurosurvival and/or neuroprotection activity of a molecule. |
| 主权项 |
1. Polypeptide, of at most 350 amino acids, comprising a cytoplasmic domain, wherein said cytoplasmic domain ends with a MAST-2 binding domain, wherein the size of said MAST-2 binding domain is from 11 to 13 amino acid residues, the first two residues of said MAST-2 binding domain are S and W, and the last four residues of said MAST-2 binding domain are Q, T, R and L, said MAST-2 binding domain being selected from the group consisting of:
(A) a sequence, whose size is 11 residues, consisting of SWX1X2X3X4X5QTRL, wherein each of X1, X2, X3, X4 and X5 is any amino acid residue (SEQ ID NO:19); (B) a sequence, whose size is 11 residues, selected from the group consisting of: SWX1KSGGQTRL (SEQ ID NO:76), SWX1SSGGQTRL (SEQ ID NO:77), SWX1SHGGQTRL (SEQ ID NO:78), SWX1SHKGQTRL (SEQ ID NO:79), SWX1SHKSQTRL (SEQ ID NO:80), SWX1HSGGQTRL (SEQ ID NO:86), SWX1HKGGQTRL (SEQ ID NO:87), SWX1HKSGQTRL (SEQ ID NO:88), SWX1SKGGQTRL (SEQ ID NO:89), SWX1SKSGQTRL (SEQ ID NO:90), SWX1SHSGQTRL (SEQ ID NO:91), SWX1SHKGQTRL (SEQ ID NO:92) and SWX1SKGGQTRL (SEQ ID NO:93), wherein X1 is any amino acid, (C) a sequence, whose size is 12 residues, consisting of SWX1X2X3X4X5X6QTRL, wherein each of X1, X2, X3, X4, X5 and X6 is any amino acid residue (SEQ ID NO:112); and (D) a sequence, whose size is 12 residues, selected from the group consisting of: SWX1HKSGGQTRL (SEQ ID NO:102), SWX1SKSGGQTRL (SEQ ID NO:103), SWX1SHSGGQTRL (SEQ ID NO:104), SWX1SHKGGQTRL (SEQ ID NO:105) and SWX1SHKSGQTRL (SEQ ID NO:106), wherein X1 is any amino acid, (E) a sequence, whose size is 13 residues, consisting of SWX1X2X3X4X5X6X7QTRL, wherein each of X1, X2, X3, X4, X5, X6 and X7, is any amino acid residue (SEQ ID NO:192), wherein said sequence does not consist of SWESHKSGGQTRL (SEQ ID NO:1), wherein said polypeptide presents a binding affinity for the PDZ domain of the human MAST2 protein which is higher than the binding affinity of rabies virus G protein comprising the SWESHKSGGQTRL (SEQ ID NO:1) sequence for the PDZ domain of the MAST2 protein. |
