用于前哨淋巴结检测的锝氮标记葡聚糖-甘露糖衍生物的设计与合成

Design and Synthesis of TcN-Labeled Dextran-Mannose Derivatives for Sentinel Lymph Node Detection.

作者信息

Boschi Alessandra, Pasquali Micòl, Trapella Claudio, Massi Alessandro, Martini Petra, Duatti Adriano, Guerrini Remo, Zanirato Vinicio, Fantinati Anna, Marzola Erika, Giganti Melchiore, Uccelli Licia

机构信息

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.

Department of Physic and Earth Science, University of Ferrara, Ferrara 44122, Italy.

出版信息

Pharmaceuticals (Basel). 2018 Jul 16;11(3):70. doi: 10.3390/ph11030070.

BACKGROUND

New approaches based on the receptor-targeted molecular interaction have been recently developed with the aim to investigate specific probes for sentinel lymph nodes. In particular, the mannose receptors expressed by lymph node macrophages became an attractive target and different multifunctional mannose derivate ligands for the labeling with Tc have been developed. In this study, we report the synthesis of a specific class of dextran-based, macromolecular, multifunctional ligands specially designed for labeling with the highly stable [Tc≡N] core.

METHODS

The ligands have been obtained by appending to a macromolecular dextran scaffold pendant arms bearing a chelating moiety for the metallic group and a mannosyl residue for allowing the interaction of the resulting macromolecular Tc conjugate with specific receptors on the external membrane of macrophages. Two different chelating systems have been selected, S-methyl dithiocarbazate [H₂N‒NH‒C(=S)SCH₃=HDTCZ] and a sequence of two cysteine residues, that in combination with a monophosphine coligand, are able to bind the [Tc≡N] core.

CONCLUSIONS

High-specific-activity labeling has been obtained by simple mixing and heating of the [Tc≡N] group with the new mannose-dextran derivatives.

背景

基于受体靶向分子相互作用的新方法最近已被开发出来，旨在研究前哨淋巴结的特异性探针。特别是，淋巴结巨噬细胞表达的甘露糖受体成为一个有吸引力的靶点，并且已经开发出了不同的用于用锝标记的多功能甘露糖衍生物配体。在本研究中，我们报告了一类专门设计用于用高度稳定的[Tc≡N]核心进行标记的基于葡聚糖的大分子多功能配体的合成。

方法

通过将带有用于金属基团的螯合部分和甘露糖基残基的侧链连接到大分子葡聚糖支架上获得配体，以使所得的大分子锝缀合物与巨噬细胞外膜上的特定受体相互作用。选择了两种不同的螯合体系，即S-甲基二硫代氨基甲酸盐[H₂N‒NH‒C(=S)SCH₃=HDTCZ]和两个半胱氨酸残基序列，它们与单膦共配体结合能够结合[Tc≡N]核心。