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1. A method for increasing nucleic acid damage of a hyperproliferating cell or for the prophylaxis or treatment of a cell proliferative disorder in a mammal having a white blood cell count within a normal range, comprising administering a peptide compound, wherein the peptide compound comprises any of the following sequences:
A) a peptide comprising residues denoted P1-P6, with the structure, P1, P2, P3, P4, P5, P6 or P6, P5, P4, P3, P2, P1;
wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), an amino acid that occupies a similar side chain space, or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, quinazoline group in the side chain;wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, an amino acid that occupies a similar side chain space, or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, or quinazoline group in the side chain;wherein P3, P4, P5 are any amino acid, or wherein one or more of P3, P4, P5 is a simple carbon chain such that the distance between P2 and P6 is about the same as the distance when each of P3, P4, P5 are amino acids;wherein P6 is Bpa, Phe4NO2, any one amino acid and Tyr, any one amino acid and Phe, any amino acid, or nothing; or B) the peptide of A), wherein the amino acid having a simple carbon chain is 11-aminoundecanoic acid, 10-aminodecanoic acid, 9-aminononanoic acid, 8-aminocaprylic acid, 7-aminoheptanoic acid, 6-aminocaproic acid, or a similar structure with one or more unsaturated carbon bonds, and/or
wherein the any one amino acid is Ser, and/orwherein P4 is Trp, and/orwherein the amino acid that occupies a similar side chain space is Tyr or Phe; or C) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6; P6, P5, P4, P3, P2, P1; P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P1, P2, P3, P4, P5, P6, P12, P11, P10, P9, P8, P7; P6, P5, P4, P3, P2, P1, P7, P8, P9, P10, P11, P12; P6, P5, P4, P3, P2, P1, P12, P11, P10, P9, P8, P7; P7, P8, P9, P10, P11, P12, P1, P2, P3, P4, P5, P6; P7, P8, P9, P10, P11, P12, P6, P5, P4, P3, P2, P1; P12, P11, P10, P9, P8, P7, P1, P2, P3, P4, P5, P6; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P6, P9, P8, P7, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; P1, P2, P7, P8, P9, P6, P11, P12; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, an amino acid that occupies a similar side chain space (e.g. d- or 1-Tyr, d- or 1-Phe), or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, or quinazoline group in the side chain;wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), or an amino acid that occupies a similar side chain space, or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, quinazoline group in the side chain;wherein P3, P4, P5 are any amino acid, or wherein one or more of P3, P4, P5 is a simple carbon chain such that the distance between P2 and P6 is about the same as the distance when each of P3, P4, P5 are amino acids;wherein P6 is Bpa, Phe4NO2, any one amino acid and Tyr, any one amino acid and Phe; andwherein at least three of P7, P8, P9, P10, P11, P12 are basic amino acids with the rest being any amino acid or absent; or D) the peptide of C), wherein the amino acid having a simple carbon chain is 11-aminoundecanoic acid, 10-aminodecanoic acid, 9-aminononanoic acid, 8-aminocaprylic acid, 7-aminoheptanoic acid, 6-aminocaproic acid, or a similar structure with one or more unsaturated carbon bonds, and/or,
wherein the any one amino acid is Ser, and/or,wherein P4 is Trp and/or,wherein the amino acid that occupies a similar side chain space is Tyr or Phe; or E) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, an amino acid that occupies a similar side chain space, or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, or quinazoline group in the side chain;wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), an amino acid that occupies a similar side chain space, or any amino acid with one or two aromatic, piperidine, pyrazine, pyrimidine, piperazine, morpholine or pyrimidine group(s), or one indole, pentalene, indene, naphthalene, benzofuran, benzothiophene, quinoline, indoline, chroman, quinoxaline, quinazoline group in the side chain;wherein P3, P4, P5 are any amino acid, or wherein one or more of P3, P4, P5 is a simple carbon chain such that the distance between P2 and P6 is about the same as the distance when each of P3, P4, P5 are amino acids;wherein P6 is Bpa, Phe4NO2, any one amino acid and Tyr, any one amino acid and Phe, any amino acid, or nothing; andwherein at least three of P7, P8, P9, P10, P11, P12 are basic amino acids with the rest being any amino acid or absent; or F) the peptide of E), wherein the amino acid having a simple carbon chain is aminoundecanoic acid or 8-aminocaprylic acid, and/or,
wherein the any one amino acid is Ser, and/or,wherein the amino acid that occupies a similar side chain space is Tyr or Phe; or G) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6 or P6, P5, P4, P3, P2, P1,
wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, Tyr, or Phe;wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, Tyr, or Phe;wherein P3 is Ser, Arg, Cys, Pro, or Asn;wherein P4 is Trp;wherein P5 is Ser, Arg, or Asn; orwherein P3, P4, P5 is a single aminoundecanoic acid or a single 8-aminocaprylic acid; andwherein P6 is Bpa, Phe4NO2, (Ser-Tyr), or (Ser-Phe); or H) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P1, P2, P3, P4, P5, P6, P12, P11, P10, P9, P8, P7; P6, P5, P4, P3, P2, P1, P7, P8, P9, P10, P11, P12; P6, P5, P4, P3, P2, P1, P12, P11, P10, P9, P8, P7; P7, P8, P9, P10, P11, P12, P1, P2, P3, P4, P5, P6; P7, P8, P9, P10, P11, P12, P6, P5, P4, P3, P2, P1; P12, P11, P10, P9, P8, P7, P1, P2, P3, P4, P5, P6; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P6, P9, P8, P7, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; P1, P2, P7, P8, P9, P6, P11, P12; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, Tyr, or Phe;wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3), Bpa, Phe4NO2, Tyr, or Phe;wherein P3 is Ser, Arg, Cys, Pro, or Asn;wherein P4 is Trp;wherein P5 is Ser, Arg, or Asn; orwherein P3, P4, P5 is a single aminoundecanoic acid or a single 8-aminocaprylic acid;wherein P6 is Bpa, Phe4NO2, (d-Ser-d-Tyr), or (d-Ser-d-Phe); and wherein at least three of P7, P8, P9, P10, P11, P12 are Arg or Lys with the rest being any amino acid or absent; or I) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha, or Nal(2);wherein P2 is (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF3);wherein P3 is Ser;wherein P4 is Trp;wherein P5 is Ser or Asn;wherein P6 is Bpa, Phe4NO2, (Ser-Tyr), or (Ser-Phe); andwherein at least three of P7, P8, P9, P10, P11, P12 are Arg with the rest being any amino acid or absent; or J) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6 or P6, P5, P4, P3, P2, P1;
wherein P1 is Cha, or Nal(2);wherein P2 is (Phe-2,3,4,5,6-F), (Phe-3,4,5F) or (Phe-4CF3);wherein P3 is Ser;wherein P4 is Trp;wherein P5 is Ser; andwherein P6 is Bpa, or (Ser-Tyr); or K) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6; P6, P5, P4, P3, P2, P1; P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P1, P2, P3, P4, P5, P6, P12, P11, P10, P9, P8, P7; P6, P5, P4, P3, P2, P1, P7, P8, P9, P10, P11, P12; P6, P5, P4, P3, P2, P1, P12, P11, P10, P9, P8, P7; P7, P8, P9, P10, P11, P12, P1, P2, P3, P4, P5, P6; P7, P8, P9, P10, P11, P12, P6, P5, P4, P3, P2, P1; P12, P11, P10, P9, P8, P7, P1, P2, P3, P4, P5, P6; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P6, P9, P8, P7, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; P1, P2, P7, P8, P9, P6, P11, P12; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha, or Nal(2);wherein P2 is (Phe-2,3,4,5,6-F), (Phe-3,4,5F) or (Phe-4CF3);wherein P3 is any amino acid;wherein P4 is d- or 1-Trp;wherein P5 is any amino acid;wherein P6 is Bpa or (Ser-Tyr);wherein P7 is Arg;wherein P8 is Arg;wherein P9 is Arg;wherein P10 is Gln or Arg;wherein P11 is Arg; andwherein P12 is d- or 1-Arg, or L) the peptide of K), wherein the any amino acid is Ser, or Pro; or M) a peptide comprising residues denoted P1-P12, with any the following structures: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, P11, P12; P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1; P12, P11, P10, P6, P9, P4, P7, P2, P1; or P1, P2, P7, P4, P9, P6, P10, P11, P12;
wherein P1 is Cha or Nal(2);wherein P2 is (Phe-2,3,4,5,6-F);wherein P3 is Ser;wherein P4 is Trp;wherein P5 is Ser;wherein P6 is Bpa or (Ser-Tyr);wherein P7 is Arg;wherein P8 is Arg;wherein P9 is Arg;wherein P10 is Gln or Arg;wherein P11 is Arg; and wherein P12 is Arg; or a prodrug thereof or a pharmaceutically acceptable salt thereof to the mammal, thereby increasing nucleic acid damage of the hyperproliferating cell or prophylaxis or treatment of the cell proliferative disorder. |
