Title of article :
Synthesis and Characterization of Dextran-Peptide-Methotrexate Conjugates for Tumor Targeting via Mediation by Matrix Metalloproteinase II and Matrix Metalloproteinase IX
Author/Authors :
Langer، Robert D. نويسنده , , Chau، Ying نويسنده , , Tan، Frederick E. نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
Abstract :
We designed and synthesized new dextran-peptide-methotrexate conjugates for tumor-targeted delivery of chemotherapeutics via the mediation of matrix metalloproteinase II (MMP-2) and matrix metalloproteinase IX (MMP-9), both being widely known tumor-associated enzymes. A robust and flexible synthesis procedure and process monitoring chromatography assays were developed. The linker chemistry and the backbone charge were optimized to allow high sensitivity of the conjugates toward the targeted enzymes. The optimal conjugate carries Pro-Val-Gly-Leu-Ile-Gly as the peptide linker, and the charge on the dextran backbone is fully neutralized. In the presence of the targeted enzymes, the peptide was cleaved and peptidyl methotrexate was released, with a kcat/Km value of 1.21 × 105 M-1 s-1 for MMP-2 and 3.60 × 103 M-1 s-1 for MMP-9, respectively. Satisfactory stability of the new conjugates was demonstrated in serum containing conditions, suggesting the conjugates can remain intact in systemic circulation. These findings supported the tumor targeting capability of the new conjugates and warranted further investigation with in vivo study.
Keywords :
Abdominal obesity , Food patterns , Prospective study , waist circumference
Journal title :
Bioconjugate Chemistry
Journal title :
Bioconjugate Chemistry