Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates
- Bioorg Med Chem Lett. 2001 Aug 6;11(15):2001-6. doi: 10.1016/s0960-894x(01)00354-7.
Affiliations
- 1. Tumor Biology Center, Clinical Research, D-79106, Freiburg, FRG. [email protected]
PMID: 11454467
DOI: 10.1016/s0960-894x(01)00354-7
Abstract
Two doxorubicin albumin conjugates (A-DP1 and A-DP2), which differ in their substrate specificity for the Matrix Metalloproteinases MMP2 and MMP9, were prepared by binding maleimide doxorubicin peptide derivatives to the cysteine-34 position of human serum albumin. The incorporated octapeptide, Gly-Pro-Gln-Arg-Ile-Ala-Gly-Gln, in A-DP2 is not cleaved by activated MMP2 and MMP9 in contrast to Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln incorporated in A-DP1 that is cleaved efficiently by activated MMP2 and MMP9 liberating a doxorubicin tetrapeptide. A-DP1 showed antiproliferative activity in a murine renal cell carcinoma line in the low micromolar range (IC(50) value approximately 0.2 microM).