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Dendrimer Functionalization with a Membrane‐Interacting Domain of Herpes Simplex Virus Type 1: Towards Intracellular Delivery
Authors:Tom P Carberry  Rossella Tarallo  Dr Annarita Falanga  Dr Emiliana Finamore  Prof Dr Massimiliano Galdiero  Prof Dr Marcus Weck  Prof Dr Stefania Galdiero
Institution:1. Molecular Design Institute and Department of Chemistry, New York University, New York, NY 10003 (USA), Fax: (+1)?212‐995‐4895;2. Dipartimeno di Scienze Biologiche, Università di Napoli “Federico II”, Via Mezzocannone 16, Napoli 80134 (Italy), Fax: (+39)?081‐253‐6642;3. Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Via de Creccio 7, Napoli 80138 (Italy)
Abstract:A poly(amide)‐based dendrimer was synthesized and functionalized with the membrane‐interacting peptide gH(625–644) (gH625) derived from the herpes simplex virus type 1 (HSV‐1) envelope glycoprotein H, which has previously been shown to assist in delivering large cargoes across the cellular membrane. We demonstrate that the attachment of the gH625 peptide sequence to the termini of a dendrimer allows the conjugate to penetrate into the cellular matrix, whereas the unfunctionalized dendrimer is excluded from translocation. The peptide‐functionalized dendrimer is rapidly taken into the cells mainly through a non‐active translocation mechanism. Our results suggest that the presented peptidodendrimeric scaffold may be a promising material for efficient drug delivery.
Keywords:click chemistry  delivery  dendrimers  membrane translocation  peptides
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