202803-47-2Relevant articles and documents
Peptide-targeted dendrimeric prodrugs of 5-aminolevulinic acid: A novel approach towards enhanced accumulation of protoporphyrin IX for photodynamic therapy
Tewari,Dondi,Yaghini,Pourzand,MacRobert,Eggleston
supporting information, (2021/02/26)
Photodynamic therapy (PDT) is a promising approach for the targeted treatment of cancer and various other human disorders. An effective, clinically approved approach in PDT involves the administration of 5-aminolevulinic acid (ALA) to generate elevated levels of the natural photosensitiser protoporphyrin IX (PpIX). The development of prodrugs of ALA is of considerable interest as a means to enhance the efficiency and cell selectivity of PpIX accumulation for PDT applications. In this work a novel peptide-targeted dendrimeric prodrug of 5-aminolevulinic acid (ALA) 13 was synthesised which displays nine copies of ALA on a core structure that is linked to a homing peptide for targeted delivery to a specific cancer cell type. The synthesis was accomplished effectively via a flexible, modular solid phase and solution phase route, using a combination of solid phase peptide synthesis and copper-catalysed azide-alkyne cycloaddition chemistry. The prodrug system shows a sustained and enhanced production of protoporphyrin IX (PpIX) in the MDA-MB-231 cell line that over-expresses the epidernal growth factor receptor (EGFR+) in comparison to equimolar ALA and the corresponding non-targeted ALA dendrimer (nine copies of ALA). This study provides a proof of concept for the development of a new generation of prodrugs for ALA-based photodynamic therapy that can deliver an enhanced ALA payload to specific tissue types.
Synthesis of hyperbranched glycodendrimers incorporating α-thiosialosides based on a gallic acid core
Meunier, Serge J.,Wu, Quigquan,Wang, Sho-Nong,Roy, Rene
, p. 1472 - 1482 (2007/10/03)
Hyperbranched glycodendrimers containing sialic acid residues were synthesized in order to further understand the multivalency effect and its role in carbohydrate-protein interactions. Gallic acid 7 as trivalent core and oligoethylene glycol derivatives as hydrophilic spacers were used to scaffold the dendritic backbones. α-Thiosialoside 16 was conjugated onto N-chloroacetylated dendritic precursors 13, 14, and 26 by nucleophilic substitution to afford trivalent 17, 18, and nonavalent 27 sialodendrimers. Complete sugar deprotection furnished water-soluble α-thiosialodendrimers 21, 22, and 29, which were used in protein-binding studies. Turbidimetric analysis confirmed the strong potential of sialodendrimers 29 having nine readily accessible sialic acid residues to bind, cross-link, and precipitate two different lectins. Preliminary results indicated that nonavalent α-sialodendrimer 29 had a greater affinity towards dimeric wheat germ agglutinin (WGA) and the lectin from the slug Limax flavus (LFA) than the corresponding trivalent glycodendrimers 21 and 22.
