Small peptides having apoptotic activities and their applications
View Patent ↗The present invention relates to nine residue peptides (M 32-40 ) from flavivirus M ectodomain able to modulate specifically the apoptotic activity of diverse flavivirus, to pharmaceutical composition comprising the same and their use for the treatment and/or the prevention of flavivirus-linked infections and cancers.
1. An isolated polypeptide having the following formula:
X1-X2-X3-X4-X5-X6-X7-X8-X9,
wherein:
X1 is absent or represents an amino acid selected from the group consisting of non-charged polar amino acids and non-polar amino acids,
X2 is absent or represents an amino acid selected from the group consisting of acidic amino acids, non-charged polar amino acids and non-polar amino acids,
X3 is selected from the group consisting of basic amino acids, non-charged polar amino acids and non-polar amino acids,
X4 is W,
X5 represents an amino acid selected from the group consisting of A, V, L, I, P, W, M and C,
X6 is selected from the group consisting of non-polar amino acids,
X7 is a basic amino acid
X8 is selected from the group consisting of basic amino acids and non-charged polar amino acids and
X9 is absent or represents an amino acid selected from the group consisting of basic amino acids and non-polar amino acids.
2. The isolated polypeptide according to claim 1 , wherein said polypeptide is selected from the group consisting of the following pro-apoptotic polypeptides:
polypeptides of 6–9 amino acids wherein X5=I, L, A;
polypeptides of 6–9 amino acids, wherein X1 is absent or represents I, V, T, X2 is absent or represents E, X3=T, S, R, N, X4=W, X5=I, A, X6=L, V, X7=R, X8=H, N, X9 is absent or represents P; and
polypeptides of 6–9 amino acids, wherein X3=T, X5=I, X6=L and X8=H.
3. The isolated polypeptide according to claim 1 , wherein said polypeptide is selected from the group consisting of the following pro-apoptotic polypeptides:
polypeptides of 6–9 amino acids wherein X5=I, L, A;
polypeptides of 6–9 amino acids, wherein X1 is absent or represents I, V, T, X2 is absent or represents E, X3=T, S, R, N, X4=W, X5=I, A, X6=L, V, X7=R, X8=H, N, X9 is absent or represents P; and
polypeptides of 6–9 amino acids, wherein X3=T, X5=I, X6=L and X8=H,
with the proviso that said polypeptide is not the polypeptide having the following sequence: IETWILRHP (SEQ ID NO.:29.
4. The isolated polypeptide according to claim 1 , wherein said polypeptide has the following sequence: IETWILRHP.
5. The isolated polypeptide according to claim 1 , wherein said polypeptide is associated with or conjugated to another polypeptide or protein such as a carrier protein or non-peptide molecule and/or incorporated into a suitable support.
6. A method of screening for molecules capable of modulating apoptosis comprising:
introducing one or more polypeptides according to claim 1 into a cell,
contacting said cell with the molecule to be screened and
detecting the presence or absence of apoptosis.
7. The new polypeptide according to claim 5 wherein the protein with which the polypeptide is associated is a carrier protein.