JBC, Vol. 253, Issue 9, 3259-3264, May, 1978
Studies on macromomycin, an antitumor protein
W. B. Im, C. K. Chiang and R. Montgomery
Macromomycin is a protein isolated from the culture filtrate of
Streptomyces macromomyceticus. It is an antibiotic and also cytotoxic to a
broad spectrum of carcinoma cells, the ID50 for P388 leukemia cells being 1
X 10(-9) M. Macromomycin binds rapidly and tightly to the P388 cell
membrane and the eventual death of the cell cannot be reversed by either
washing the toxin away or treating the cell with trypsin. The cytotoxicity
does not appear to be specific for any phase of the P388 cell cycle.
Macromomycin is a single polypeptide, pI 5.38, devoid of methionine and
arginine residues and contains 4 cysteine residues joined by two
intramolecular disulfide bonds. The cytotoxicity results in inhibition of
DNA, RNA, and protein synthesis in P388, the latter inhibition occurring a
few hours after the inhibition of nucleic acid synthesis. The antibiotic
and antitumor activities are destroyed rapidly by ultraviolet light, which
gives a product that differs little in amino acid composition, molecular
weight, and antigenic property, but can be separated from the native
macromomycin by ion exchange chromatography. It is proposed that
macromomycin has an ultraviolet-sensitive prosthetic group upon which much
of the biological activity is based.
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