Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates. |
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Authors: | F Kratz J Drevs G Bing C Stockmar K Scheuermann P Lazar C Unger |
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Affiliation: | Tumor Biology Center, Clinical Research, D-79106, Freiburg, FRG. felix@tumorbio.uni-freiberg.de |
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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). |
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