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Monday, 12 September, 2011

Solid-Phase Synthesis of Sequence-Defined T-, i-, and U-Shape Polymers for pDNA and siRNA Delivery

D. Schaffert, C. Troiber, E. E. Salcher, T. Fröhlich, I. Martin, N. Badgujar, C. Dohmen, D. Edinger, R. Kläger, G. Maiwald, K. Farkasova, S. Seeber, K. Jahn-Hofmann, P. Hadwiger, E. Wagner -
Angew. Chem. Int. Edition, Vol. 50 (38), pp. 8986-8989, 2011

Viral proteins are far more effective in mediating the transport of viral nucleic acids into cells than the currently available synthetic polymers for gene transfer. To mimic viral delivery processes, functional domains such as endosomolytic agents and targeting ligands have been conjugated to polymers. The chemistry of such conjugates, however, lacks the molecular precision of sequence-defined viral proteins, regarding both the polydispersity of the polymer and the conjugation sites. The common practice to apply such polydisperse mixtures in transfections may obscure accurate structure–activity relationships. It is questionable whether polydisperse macromolecules will ever compete successfully with their viral counterparts. Herein we communicate on the solid-phase-supported synthesis of a small library of sequence-defined polymers and their use for pDNA and siRNA delivery.

 

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