2. Academic Validation
  3. Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates

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.
F Kratz 1,  J Drevs,  G Bing,  C Stockmar,  K Scheuermann,  P Lazar,  C Unger
Affiliations

Affiliation

  • 1 Tumor Biology Center, Clinical Research, D-79106, Freiburg, FRG. felix@tumorbio.uni-freiberg.de
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).

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