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 fur the matrix metalloproteinases MMP2 and MMP9. wer e prepared by binding maleimide doxorubicin peptide derivatives to the cyst eine-34 position of human serum albumin. The incorporated octapeptide, Gly- Pro-Gln-Arg-Ile-Ala-Giy-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 t hat is cleaved efficiently by activated MMP2 and MMP9 liberating a doxorubi cin tetrapeptide. A-DP1 showed antiproliferative activity in a murine renal cell carcinoma line in the low micromolar range (IC50 value approximate to 0.2 muM). (C) 2001 Elsevier Science Ltd. All rights reserved.