A viable strategy for screening the effects of glycan heterogeneity on target organ adhesion and biodistribution in live mice

Abstract

This work represents the first broad study of testing diverse heterogenous glycoconjugates (7 different glycoalbumins) for their differential in vivo binding (11 different cancer cell types) in both cell- and animal-based studies. As a result, various changes in biodistribution, excretion, and even tumor adhesion were observed.

A Strategy for Tumor Targeting by Higher‐Order Glycan Pattern Recognition: Synthesis and In Vitro and In Vivo Properties of Glycoalbumins Conjugated with Four Different N‐Glycan Molecules

“…The glycoclusters' capability to bind cells was determined via TAMRA fluorescence. As we observed with most of the glycoalbumins so far investigated, [4] our glycoalbumins internalized into the cells (representative microscopy image in Figure S34 in the Supporting Information). But for our cell targeting purposes, it does not matter whether glycoalubumins internalize or not.…”

Heteroglycoclusters With Dual Nanomolar Affinities for the Lectins LecA and LecB From Pseudomonas aeruginosa

“…So far, several heterovalent structures have been reported for studying the interaction process with a large class of carbohydrate-specific proteins (i.e., glycosidases, glycosyltransferases, lectins, antibodies) (Deguise et al, 2007; Ortega-Muñoz et al, 2009; Gómez-García et al, 2010; Lindhorst et al, 2010; Karskela et al, 2012; Abellán Flos et al, 2016; Vincent et al, 2016; Ortiz Mellet et al, 2017; Gade et al, 2018; Ogura et al, 2018) or for triggering multifaceted immune response against tumor cells (Ragupathi et al, 2002; Zhu et al, 2009; Pett et al, 2017). These studies highlight the complexity of heterocluster effects and reinforce the need of new structures to go one step further toward the understanding of naturally occurring recognition events and the development of more active compounds.…”

Revealing biomedically relevant cell and lectin type-dependent structure–activity profiles for glycoclusters by using tissue sections as an assay platform

“…This favourable aspect is also a part of the in vivo studies with labelled neoglycoproteins presenting natural and synthetic glycans up to custom-made microheterogeneity used for targeting and imaging. [83][84][85][86][87][88][89] On the side of the proteins, mimicking the natural occurrence of lectins in mixtures, in terms of constituents and relative concentrations, will enable to trace currently not well-dened consequences of competition for binding sites and crossreactivity of glycoclusters among lectins. Given the assay's reliability and sensitivity as well as its use with any type of tissue, its application is advised, prior to considering testing glycoclusters in vivo, for example to minimise such overlaps in target binding by iterative structural renements including headgroup chemistry.…”