Peptides and peptidomimetics having anti-proliferative activity and/or that augment nucleic acid damaging agents or treatments

Abstract

This invention provides compounds including peptides and peptidomimetics that can be used to treat cell proliferative disorders, such as those associated with benign and malignant tumor cells. While the invention is not limited to any particular mechanism, the compounds of the invention appear to function at least in part by inhibiting G2 cell cycle checkpoint. Thus, invention compounds can be used to inhibit cell growth alone or be used in combination with a nucleic acid damaging treatment to inhibit cell growth.

1 - 16 . (canceled) 
     
     
         17 . A contiguous peptide or peptidomimetic sequence comprising the following structure:
 P6, P5, P4, P3, P2, P1, P7, P8, P9, P10, P11, P12 (SEQ ID NO:25); P6, P5, P4, P3, P2, P1, P12, P1, P10, P9, P8, P7 (SEQ ID NO:26); P7, P8, P9, P10, P1, P12, P1, P2, P3, P4, P5, P6 (SEQ ID NO:27); P7, P8, P9, P10, P11, P12, P6, P5, P4, P3, P2, P1 (SEQ ID NO:28); P12, P11, P10, P9, P8, P7, P1, P2, P3, P4, P5, P6 (SEQ ID NO:29); P12, P11, P10, P9, P8, P7, P6, P5, P4, P3, P2, P1 (SEQ ID NO:30); P12, P11, P6, P9, P8, P7, P2, P1 (SEQ ID NO:31); P12, P11, P10, P6, P9, P4, P7, P2, P1 (SEQ ID NO:32); P1, P2, P7, P8, P9, P6, P11, P12 (SEQ ID NO:33); or P1, P2, P7, P4, P9, P6, P10, P11, P12 (SEQ ID NO:34);   wherein P1 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF 3 ), Bpa, Phe4NO2, Tyr, or Phe;   wherein P2 is Cha, Nal(2), (Phe-2,3,4,5,6-F), (Phe-3,4,5F), (Phe-4CF 3 ), 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; or   wherein 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.   
     
     
         18 - 24 . (canceled) 
     
     
         25 . The peptide or peptidomimetic sequence of  claim 17 , wherein one or more residues is 1-type. 
     
     
         26 . The peptide or peptidomimetic sequence of  claim 17 , wherein one or more residues is d-type. 
     
     
         27 . (canceled) 
     
     
         28 . The peptide or peptidomimetic sequence of  claim 17 , wherein the sequence inhibits proliferation of a cell. 
     
     
         29 . The peptide or peptidomimetic sequence of  claim 17 , wherein the sequence abrogates cell cycle G2 checkpoint of a cell. 
     
     
         30 . The peptide or peptidomimetic sequence of  claim 17 , wherein the sequence has a length from about 6 to about 12, 10 to about 20, 18 to about 25, 25 to about 100, 25 to about 200, or 50 to about 300 residues in length. 
     
     
         31 . A composition comprising the peptide or peptidomimetic sequence of  claim 17  and a nucleic acid damaging agent. 
     
     
         32 . A composition comprising the peptide or peptidomimetic sequence of  claim 17  and an anti-proliferative agent. 
     
     
         33 . A pharmaceutical composition comprising the peptide or peptidomimetic sequence of  claim 17 . 
     
     
         34 . A pharmaceutical composition comprising the peptide or peptidomimetic sequence of  claim 17  and a nucleic acid damaging agent or an anti-proliferative agent. 
     
     
         35 . A kit comprising the peptide or peptidomimetic sequence of  claim 17  and instructions for use. 
     
     
         36 . The kit of  claim 35 , wherein the instructions for use include instructions for inhibiting cell proliferation in combination with a nucleic acid damaging treatment. 
     
     
         37 . The kit of  claim 35 , further comprising a nucleic acid damaging agent. 
     
     
         38 . The kit of  claim 35 , further comprising an anti-proliferative agent. 
     
     
         39 - 65 . (canceled)