Cancer inhibitory peptides

• US 5,599,902 A
• Filed: 11/10/1994
• Issued: 02/04/1997
• Est. Priority Date: 11/10/1994
• Status: Expired due to Term

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Pettit, George R., Srirangam, Jayaram K.
• Primary Examiner(s): Woodward, Michael P.
• Assistant Examiner(s): Prickril, Benet
• Application Number:
  US08/338,004
• Time in Patent Office: 817 Days
• Field of Search: 530/330, 530/331, 514/17, 514/18
• US Class Current: 530/330
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07K 5/0205 containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
• CPC Class Codes: C07K 7/02 Linear peptides containing at least one abnormal peptide link

Abstract

The sea hare Dolabella auricularia has yielded many structurally distinct ptides which possess antineoplastic activity. Presently the compound denominated "dolastatin 10" represents the most important of such peptides because of its demonstrated potential as an anticancer drug.

The present invention relates to the systematic creation of seven unique pentapeptides by selectively coupling a tripeptide-trifluoroacetate salt with a preselected dipeptide trifluoroacetate salt which provide active molecules capable of emulating the measured therapeutic effect of dolastatin 10.

Claims

1. A composition of matter having the structural formula:

##STR4## wherein;

R₁ is selected from the group consisting of;

##STR5## R₂ is selected from the group consisting of;

##STR6## and R₃ is selected from the group consisting of hydrogen and methyl.

3. A composition of matter according to claim 1 wherein R₁ is:

##STR8## and R₂ is;

##STR9##

4. A composition of matter according to claim 1 wherein R₁ is:

##STR10## and R₂ is;

##STR11## and R3 is selected from the group consisting of hydrogen and methyl.

5. A composition of matter according to claim 1 wherein R₁ is:

##STR12## and R₂ is;

##STR13##

6. A composition of matter according to claim 1 wherein R₁ is:

##STR14## and R₂ is;

##STR15##

7. A composition of matter according to claim 1 wherein R₁ is:

##STR16##

2. A composition of matter having the structural formula:

##STR7##