Noninvasive Imaging of Dendrimer‐Type N‐Glycan Clusters: In Vivo Dynamics Dependence on Oligosaccharide Structure

Abstract

Ganzkörperaufnahme: Eine selbstaktivierende 1,3‐dipolare Huisgen‐Cycloaddition und eine 6π‐Azaelektrocyclisierung von Lysin‐haltigen Dendrimeren (siehe Bild) ermöglichen die Visualisierung der In‐vivo‐Dynamik und organspezifischen Anreicherung von N‐Glycanen. Über Strukturvarianten der N‐Glycane lässt sich der Ganzkörpertransport des Clusters in Nacktmaus‐ und Krebsmodellen steuern.

Cell surface and in vivo interaction of dendrimeric N-glycoclusters

“…1 and 2) [12]. These clusters are structurally characterized by 16 molecules of varying N-glycan derivatives (1a-c), as well as a terminal lysine ε-amino group for incorporation of either a fluorescent label or positron emission tomography (PET) radiolabel (ie/ 68 Ga-1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA).…”

“…In general, a single molecule of Fig. 2 Preparation of dendrimeric N-glycoclusters through histidine-accelerated Cu(I)-mediated Huisgen 1,3-dipolar cycloaddition and labeling by 6π-azaelectrocyclization [12] the glycans (monomeric glycan) is not suitable as an imaging probe due to its small size and weak interactions with sugar binding proteins in vivo [22,23]. As a consequence, they will not accumulate in specific organs, but be rapidly excreted from the kidney via biofiltration.…”

“…2), in the presence of equimolar amounts of copper sulfate and diisopropylethylamine, as well as 3 equivalents of Fig. 1 Structures of dendrimeric N-glycoclusters [12,13] sodium ascorbate (all relative to the N-glycan molecules) at room temperature for 20 min. Residual copper ions were removed by DOTA chelation and size-partitioning centrifugal filtration.…”

“…The new Nglycoclusters, which contain 16 molecules of various N-glycan molecules, were efficiently prepared by the histidinemediated Huisgen cycloaddition. Application of these clusters not only allowed detection of platelet endothelial cell adhesion molecule (PECAM) on human umbilical vein endothelial cells (HUVEC) as a α(2-6)-sialylated oligosaccharides recognizing lectin [13], but when intravenously injected into mice, was also shown to control organ-selective accumulation and possess differential serum clearance properties based on Nglycan structures [12].…”

“…In this personal account, we wish to describe the synthesis, and in vitro/in vivo properties of lysinebased dendric N-glycoclusters ( Fig. 1) [12]. The new Nglycoclusters, which contain 16 molecules of various N-glycan molecules, were efficiently prepared by the histidinemediated Huisgen cycloaddition.…”