Peptides having a cyclic structure and restoring the...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/82 (2006.01) C07K 7/08 (2006.01) C07K 7/52 (2006.01) C07K 7/64 (2006.01) C07K 14/47 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2289960

Peptides having cyclic structures represented by the following general formula (I): R1(X1)n1(X2)n2(X3)n3(X4)n4(X5)n5(X6)n6(X7)n7(X8)n8(X9)n9(X10)n10(X11)n11(X12)n1 2(X13)n13(X14)n14(X15)n15(X16)n16(X17)n17R2 and exerting the effect of restoring a P53 protein activity on P53 protein mutants or pharmacologically acceptable salts thereof. In said formula (I) Xi means an arbitrary member selected from among X1 to X17 while ni means an arbitrary member selected from among n1 to n17 (provided that i is an integer of from 1 to 17), then Xi represents an amino acid residue or an organic acid residue; a functional group in a residue Xp selected among X1 to X11 (provided that p is an integer of from 1 to 11) and a functional group Xq selected from among X8 to X17 (provided that q is an integer of from 8 to 17 and larger than p) form a cyclic structure having a crosslinkage selected from among S-S, S-CH2-S, S-CH2- C6H4-CH2-S, S-CH2-CO, CO-NH, NH-CO, O-CO or CO-O; R1 represents optionally substituted alkanoyl, etc.; and R2 represents optionally substitued alkoxy, etc.

L'invention concerne des peptides à structures cycliques représentés par la formule générale ci-après (I): R?1¿(X?1¿)?n1¿(X?2¿)?n2¿(X?3¿)?n3¿(X?4¿)?n4¿(X?5¿)?n5¿(X?6¿)?n6¿(X?7¿)?n7¿(X?8¿)?n8¿(X?9¿)?n9¿(X?10¿)?n10¿(X?11¿)?n11¿(X?12¿)?n12¿(X?13¿)?n13¿(X?14¿)?n14¿(X?15¿)?n15¿(X?16¿)?n16¿(X?17¿)?n17¿R?2¿ et ayant un effet restaurateur de l'activité de la protéine P53 sur les mutants de ladite protéine, ou des sels pharmaceutiquement acceptables desdits peptides. Dans ladite formule, lorsque X?i¿ est un élément arbitraire choisi entre X?1¿ et X?17¿ tandis que n?i¿ est un élément arbitraire choisi entre n?1¿ et n?17¿ (à condition que i soit un entier allant de 1 à 17), X?i¿ représente un résidu d'acide aminé ou d'acide organique; un groupe fonctionnel à l'intérieur d'un résidu X?p¿ choisi dans l'éventail X?1¿ - X?11¿ (à condition que p soit un entier allant de 1 à 11) et un groupe fonctionnel X?q¿ choisi dans l'éventail X?8¿ - X?17¿ (à condition que q soit un entier allant de 8 à 17 et supérieur à p) forment une structure cyclique à une liaison réticulée choisie parmi S-S, S-CH¿2?-S, S-CH¿2?-C¿6?H¿4?-CH¿2?-S, S-CH¿2?-CO, CO-NH, NH-CO, O-CO ou CO-O; R?1¿ représente alcanoyle éventuellement substitué, etc; et R?2¿ représente alcoxy éventuellement substitué, etc.

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