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Updated: Jun 10, 2026
Targeted Antibody Blocking by a Dual-Functional Conjugate of Antigenic Peptide and Fc-III Mimetics (DCAF)
Published on: September 17, 2019
RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can
Daniel Q McNerny1, Jolanta F Kukowska-Latallo, Douglas G Mullen
1Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Chemical Engineering, Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
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 αvβ3 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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