Synthesis of highly controlled carbohydrate–polymer based hybrid structures by combining heparin fragments and sialic acid derivatives, and solid phase polymer synthesis

Abstract

Heparin is a polymeric carbohydrate with a variety of biomedical applications that is particularly challenging from a synthetic point of view. Here, we present the synthesis of carbohydrate-polymer based hybrid structures by combining defined heparin fragments with monodisperse, sequence-controlled glycooligo(amidoamines) suitable as glycan mimetic model compounds of heparin as demonstrated by STD-NMR binding studies with viral capsids.

Divalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers

“…[6a,8] For on‐resin attachment of sialic acid derivatives to oligoamide scaffolds presenting either azide or alkyne side chains, functionalized Neu5Ac derivatives Neu5Ac‐Prop ( 1 ) and Neu5Ac‐N 3 ( 2 ) were first synthesized following established protocols . 3′‐SL‐Prop ( 3 ) was obtained following our previously reported protocol . Although the chemical shifts of the 1 H‐NMR signals of the sialic acid derivatives 1 and 2 are in line with already published data for α‐anomer compounds, some uncertainty about the absolute configuration of the synthesized molecules remains.…”

“…Specifically, we used previously established building blocks introducing either an azide or alkyne functionality in the side chain of the oligomeric scaffold, which allow for functionalization with different sialic acid derivatives via copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC). [6a,8] For on‐resin attachment of sialic acid derivatives to oligoamide scaffolds presenting either azide or alkyne side chains, functionalized Neu5Ac derivatives Neu5Ac‐Prop ( 1 ) and Neu5Ac‐N 3 ( 2 ) were first synthesized following established protocols . 3′‐SL‐Prop ( 3 ) was obtained following our previously reported protocol .…”

Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers

“…In contrast to natural polysaccharides, synthetic glycomimetics are defined, homogeneous, replicable, and tunable compounds that can be designed to vary in length, size, and presentation. In addition, different sugars, linkers, and spacings can also be explored. − Moreover, glycomimetics provide the advantage that they have, to the best of our knowledge, no further bioactive properties avoiding, for example, the anticoagulating properties of heparin in vivo, which may cause inherent risks for certain applications. While the incorporation of different sugars into glycopolymers had only slight effects on their efficacy in this study, it has been previously noted that optimization of aspects such as length, composition, and delivery may yield increased biological function beyond that of the natural ligands .…”

Low-Dispersity Polymers in Ab Initio Emulsion Polymerization: Improved MacroRAFT Agent Performance in Heterogeneous Media

“…Attempts to synthetically imitate this level of sequence control have thus far eluded chemists. [4][5][6][7] Advances have been seen in the form of the development of Single Unit Monomer Insertion, 8 which take advantage of differing bond stability to add precisely one monomer unit into a growing chain. This procedure is however synthetically laborious and at this stage only suitable for short oligomers.…”

“…Well-defined polymers are ubiquitous within biological systems, serving a range of functions from catalysis, in the case of enzymes, to providing the structural support of chitosan exoskeletons. − In the majority of cases, the monomer sequences in these biopolymers are finely controlled. Attempts to synthetically imitate this level of sequence control have thus far eluded chemists. − Advances have been seen in the form of the development of single-unit monomer insertion, which takes advantage of differing bond stabilities to add precisely one monomer unit into a growing chain. This procedure is, however, synthetically laborious and, at this stage, only suitable for short oligomers.…”