Synthesis of Sphere-Type Monodispersed Oligosaccharide−Polypeptide Dendrimers

Abstract

A sphere-type fully substituted oligosaccharide-β-alanine-poly(lysine) dendrimer having a sharp molecular weight distribution was synthesized. Sphere-type poly(lysine) dendrimers were prepared using 1,4-diaminobutane as an initiator core and N,N′-bis(tert-butyloxycarbonyl)-L-lysine as a branching unit. β-Alanine was bound to the poly(lysine) dendrimer generation 3 to form β-alanine-poly(lysine) dendrimer generation 3, which has 16 terminal amino groups on its surface. A series of sphere-type oligosaccharide-β-alanine-poly(lysine) dendrimers were obtained by binding such an oligosaccharide as maltose, lactose, cellobiose, maltotriose, or a mixture of lactose and maltose to the surface of the β-alanine-poly(lysine) dendrimer scaffolding by reductive amination using the borane-pyridine complex. Oligosaccharide-β-alanine-poly(lysine) dendrimers having 32 oligosaccharide residues were obtained in high yields. NMR and MALDI-TOF mass measurements revealed that the oligosaccharide-polypeptide dendrimers have a monodispersed molecular weight distribution, the molecular weight of which was 13 418.36, 13 472.50, and 13 507.28 g/mol for cellobiose, maltose, and lactose, respectively, indicating that a complete substitution of the amino group by the oligosaccharide occurred.

Synthesis of New Spherical Polylysine Oligosaccharide Dendrimers with C6 Methylene Spacer

“…Scheme 1 indicates the synthesis route of the cellobiose-C6 spacer-polylysine dendrimer third generation ( ). According to our previous papers [8,18], 1, 4-diaminobutane was condensed with di-boc-lysine by BOP and DIEA reagents to give a first generation lysine dendrimer ( ) in 75% yield. After removal of the boc groups, di-boc-lysine was repeatedly condensed and the boc-protected groups deprotected with 2N TFA to give second and third generation polylysine dendrimers ( ) and ( ) in 82% and 83% yields from ( ) and ( ), respectively.…”

“…Previously, we reported the synthesis of a spheretype polylysine dendrimer with a maltose unit by reductive amination between the maltose reducing end and the terminal amino group of the dendrimer [8]. It was revealed that all amino groups in the polylysine dendrimer having 16 amino groups were completely replaced by maltose to give a polylysine dendrimer having 32 maltose units.…”

“…It was revealed that all amino groups in the polylysine dendrimer having 16 amino groups were completely replaced by maltose to give a polylysine dendrimer having 32 maltose units. Although the reductive amination worked effectively to introduce a sugar moiety, one glucose residue of the reducing end of maltose was decomposed by the reduction of a borane pyridine complex [8,19]. In this work, we connected the cellobiose unit ( ) to the terminal amino group of the polylysine dendrimers without decomposition of the cellobiose structure through the C6 methylene spacer, a method that effectively withdrew the functionality of oligosaccharides without decomposing the sugar structure.…”

Synthesis of Structurally‐Controlled AIDS Vaccine Model with Glyco‐Peptide Dendrimer Scaffolds

“…We synthesized sugar-containing poly(lysine) dendrimers for an HIV vaccine by directly introducing lactose, maltose, cellobiose or maltotriose to poly(lysine) dendrimer through a simple reductive amination. [36][37][38] Fully substituted, sugar-containing poly(lysine) dendrimers were obtained when activation of terminal amino group was performed. [37] In this kind of sugar-containing dendrimers, the nonreducing sugar residue is directed outwards.…”

“…[36][37][38] Fully substituted, sugar-containing poly(lysine) dendrimers were obtained when activation of terminal amino group was performed. [37] In this kind of sugar-containing dendrimers, the nonreducing sugar residue is directed outwards.…”