Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochemistry. 1994 Oct 25;33(42):12540-5.

Marked interspecies variations concerning the interactions of camptothecin with serum albumins: a frequency-domain fluorescence spectroscopic study.

Author information

1
Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus 43210-1291.

Abstract

Camptothecin, an anticancer agent reknown for its novel mechanism of action and outstanding murine in vivo activity, has to date displayed only modest therapeutic utility against human cancers. The drug contains an delta-lactone ring moiety which, at pH7.4, hydrolyzes to yield a biologically inactive carboxylate form. Comparison of drug stability in both plasma and purified serum albumin samples revealed that ring opening occurred to a much greater extent in human samples versus those of other species. Multifrequency phase-modulation spectroscopic analyses of the intrinsic fluorescence emissions of the two drug forms revealed a physical explanation for the extensive ring opening observed in the presence of human serum albumin (HSA): the protein exhibited a marked 200-fold binding preference for the carboxylate (K = 1.2 x 10(6) M-1) relative to the lactone (K approximately 5.5 x 10(3) M-1). Serum albumins from other species were found to bind camptothecin carboxylate not nearly as tightly as HSA. Due to the unique capacity of human albumin to bind camptothecin carboxylate, resulting in extensive conversion of the drug to its biologically inactive form, it appears that the success of the agent in eradicating cancer in animal models may be inherently more difficult to duplicate in man.

PMID:
7918477
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center