Development and in vitro efficacy of novel MMP2 and MMP9 specific doxorubicin albumin conjugates

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 (IC50 value≈0.2 μM).

Two doxorubicin albumin conjugates (A-DP1 and A-DP2) incorporating octapeptides, which differ in their substrate specificity for the matrix metalloproteinases MMP2 and MMP9, were prepared. A-DP1 was cleaved efficiently by MMP2 and MMP9 and exhibited in vitro activity in the low micromolar rangeFigure optionsDownload as PowerPoint slide