Synthesis of Biotinylated Multipodal Glycoclusters on a Solid Support

Abstract

Trivalent glycoconjugates, each bearing a biotin side arm in addition to three different sugar ligands, have been synthesized on a solid support. The conjugates were assembled on an orthogonally protected pentaerythrityl tetramine core that was anchored to the support through a backbone amide linker. Peptide coupling chemistry was applied to elongate three of the branches with β‐alanine and a fully acylated glycosylacetic acid. The fourth branch was levulinoylated and oximated with aminooxy‐derivatized D‐biotin, followed by acidolytic release into solution. The acyl protecting groups were removed by methoxide‐catalyzed transesterification in methanol.

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.…”