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RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.

ABSTRACT: 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 ?v?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.

SUBMITTER: McNerny DQ

PROVIDER: S-EPMC2920625 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.

McNerny Daniel Q DQ Kukowska-Latallo Jolanta F JF Mullen Douglas G DG Wallace Joseph M JM Desai Ankur M AM Shukla Rameshwer R Huang Baohua B Banaszak Holl Mark M MM Baker James R JR

Bioconjugate chemistry 20091001 10

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 αvβ3 integrin expressing human umbilical vein endothelial cells (HUVEC) and human glioblastoma cells (U87MG) ...[more]

PMID: 20711425

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Dataset Information

RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.

Publications

RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.

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