Platinum bound to transferrin for use in the treatment of breast

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...

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530402, 424101, 424649, 514 6, C07K 1506, A61K 3702, A61K 3514, A61K 3324

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active

RE0330710

ABSTRACT:
A method of preparing an anti-breast tumor compound comprised of a toxic metal bound to the blood protein transferrin is disclosed which has superior therapeutic properties. When monomeric transferrin is bound to cis-Dichlorodiammineplatinum (II), a chemotherapeutic agent is produced which specifically attacks and kills rapidly multiplying breast tumor cells without damaging normal cells. In addition, the body's immune defenses against foreign substances are substantially not activated. In preferred embodiments, 1.8-2.2 atoms of platinum are bound to each molecule of transferrin. The platinum-transferrin is prepared by first protecting the sulfhydro groups on essentially iron free transferrin with an excess of cystine in solution. Cis-dichlorodiamine platinum (II) is then reacted with the iron-free transferrin in the presence of bicarbonate anion. The platinum transferrin is dialyzed to remove the weak organic acid and bicarbonate anion, and then passed through molecular sieves to separate the monomeric product which is thereafter concentrated to a therapeutically useful concentration.

REFERENCES:
Stjernholm et al, Bioinorganic Chem. 9, pp. 277-280 (1978).
Bodanszky et al, in The Peptides, vol. 5 (1983) p. 156.
Aisen et al, J. Biol. Chem. 244, No. 17 (1969) pp. 4628-4633.
Rosenberg et al, J. Biol. Chem. 242, No. 6 (1967) pp. 1347-1352.
Gullo et al, Cancer Chemother. Pharmacol., 5, (1980), pp. 21-26.
Stjernholm et al, "The Binding of Platinum to Human Transferrin", Bioinorganic Chem., 9, 277-280 (1978).
Bodansky et al, "Side Reactions in . . . ", in The Peptides, vol. 5, Gross et al. eds, 1983, p. 156.
Aisin et al., "The Chronium, Magnesium and Cobalt Complexes of Transferrin", J. Biol. Chem., 244, No. 17, pp. 4628-4633.

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