Pentapeptides as antitumor agents

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 4 to 5 amino acid residues in defined sequence

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514 17, C07K 700

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active

057418926

ABSTRACT:
The present invention provides anti-tumor peptides of Formula I,

REFERENCES:
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patent: 5504191 (1996-04-01), Pettit et al.
patent: 5530097 (1996-06-01), Pettit et al.
Pettit, G. R., et al., "Antineoplastic Agents 337. Synthesis of Dolastatin-10 Structural Modifications," Anti-Cancer Drug Design, 10: 529-544 (1995).
Miyazaki, K., et al., "Synthesis and Antitumor Activity of Novel Dolastatin-10 Analogs," Chem. Pharm. Bull., 43(10) : 1706-1718 (1995).
Pettit, G.R. et al., "Isolation of Dolastatins 10-15 From the Marine Mollusc Dolabella Auricularia," Tetrahedron, 49(41):9151-9170 (1993).
Pettit, G.R., et al., "The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15," Tetrahedron, 50(42):12097-12108 (1994).
Pettit, G.R., et al., "The Isolation and Structure of a Remarkable Marine Animal Antineoplastic Constituent: Dolastatin 10", J. Am. Chem. Soc. 109: 6883-6885 (1987).
Bai, R., et al., "Structure-Activity Studies with Chiral Isomers and with Segments of the Antimitotic Marine Peptide Dolastatin 10", Biochemical Pharmacology 40(8): 1859-1864 (1990).
Pettit, G. R, et al., "Antineoplastic Agents. 220. Synthesis of Natural (-)-Dolastatin 15", J. Am. Chem. Soc., 113: 6692-6693 (1991).
Pettit, G. R., et al., "Isolation and Structure of the Cytostatic Linear Depsipeptide Dolastatin 15", J. Org. Chem., 54: 6005-6006 (1989).
Bai, R., et al., "Dolastatin 15, a potent antimitotic depsipetide derived from Dolabella auricularia. Interaction with tubulin and effects on cellular microtubules", 1-Pharmacology Abstract 117: 103735g p. 41 (1992).
Pettit, G. R., et al., "Isolation and Structure of the Cytostatic Depsipeptide Dolastatin 13 from the Sea Hare Dolabella auricularia", J. Am. Chem. Soc., 111(13): 5015-5017 (1989).

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