Journal
BIOCONJUGATE CHEMISTRY
Volume 20, Issue 10, Pages 1853-1859Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc900217h
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Funding
- National Cancer Institute
- National Institutes of Health [1 R01 CA119409]
- NATIONAL CANCER INSTITUTE [R01CA119409] Funding Source: NIH RePORTER
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Poly(amidoamine) (PAMAM) dendrons were synthesized with c(RGDyK) peptide on the surface to create a scaffold for cellular targeting and multivalent binding. Binary dendron-RGD conjugates were synthesized with a single Alexa Fluor 488, biotin, methotrexate drug molecule, or additional functionalized dendron at the focal point. The targeted dendron platform was shown to specifically target alpha(V)beta(3) integrin expressing human umbilical vein endothelial cells (HUVEC) and human glioblastoma cells (U87MG) in vitro via flow cytometry. Specific targeting of the dendron-RGD platform was further confirmed by confocal microscopy. Biological activity of the targeted drug conjugate was confirmed via XTT assay. The orthogonal reaction chemistry used at the dendron focal point gives a precise 1:1 ratio of the attachment of multiple functionalities to a small-molecular-weight, chemically stable, high avidity molecule. These studies serve as-a framework to selectively combine biologically relevant functions with enhanced specific binding activity to: substitute for antibodies in many diagnostic and therapeutic applications.
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