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Cancer Chemother Pharmacol. 1993;32(2):109-15.

Identification of serum components that inhibit the tumoricidal activity of amphiphilic alpha helical peptides.

Author information

1
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.

Abstract

Antimicrobial peptides that can form amphiphilic alpha helices were tested for their ability to lyse various human tumor cell lines in vitro. These peptides include C18G, whose sequence is a derivative of the carboxyl terminus of human platelet factor IV, and 399, an idealized amphiphilic alpha helix. Both peptides exhibited potent antitumor activity against all cell lines tested, unlike magainin 2, a naturally occurring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions. Also, the lytic activity of C18G is specific for tumor cells versus human red blood cells. The effects of serum can be important when evaluating the potency of lytic peptides, since other tumoricidal peptides have been shown to be completely inactivated by low serum levels. Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations. Various serum components were tested for their inhibitory activity. Whereas albumin and high-density lipoprotein had only slight inhibitory properties, low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis. The peptide 399, which is more sensitive to serum inhibition than C18G, also binds more extensively to all serum components tested.

PMID:
8485805
DOI:
10.1007/bf00685612
[Indexed for MEDLINE]

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