ABSTRACT
Solid phase synthesis (SPS) is well established for the synthesis of biomacromolecules such as peptides, oligonucelotides, and oligosaccharides, and today is also used for the synthesis of synthetic macromolecules and polymers. The key feature of this approach is the stepwise assembly of building blocks on solid support, enabling monodispersity and monomer sequence control. However, in order to achieve such control, a high excess of building blocks is required during the reaction. Herein, the recovery, purification, and reusability of building blocks used in SPS, including representative examples of tailor-made building blocks, Fmoc-protected amino acids, and functionalized carbohydrate ligands, are reported for the first time. Results demonstrate the general applicability with recovery in high yields and high purity. Furthermore, the described recovery process can be applied in both manual and automated synthesis using a standard peptide synthesizer. Overall, this process is envisioned to be applicable for a large variety of building blocks used in the SPS of different types of molecules, and to contribute to more resourceful SPS syntheses.
Subject(s)
Polymers/chemistry , Solid-Phase Synthesis Techniques/methods , Amino Acids/chemistry , Carbohydrates/chemistry , Glycosides/chemistry , Ligands , Molecular Structure , Peptides/chemical synthesis , RecyclingABSTRACT
The synthesis of brush glycopolymers mimicking the architecture of proteoglycans is achieved by grafting sequence-defined glycooligomers derived from solid-phase polymer synthesis onto a poly(active ester) scaffold. This approach gives access to a first library of brush glycopolymers with controlled variations in the degree of branching and number of carbohydrate ligands per branch. When studying lectin binding of linear and brush glycopolymers to lectins Concanavalin A (ConA), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and mannose-binding lectin (MBL), different preferences are observed with MBL showing higher binding to linear glycopolymer and ConA and DC-SIGN favoring brush glycopolymers. This finding suggests that the architecture of polymeric glycan mimetics affects binding to lectins not only in terms of creating higher avidity but potentially also selectivity ligands.
Subject(s)
Cell Adhesion Molecules/metabolism , Concanavalin A/metabolism , Lectins, C-Type/metabolism , Mannose-Binding Lectins/metabolism , Receptors, Cell Surface/metabolism , Animals , Catalysis , Cell Adhesion Molecules/chemistry , Concanavalin A/chemistry , Copper/chemistry , Lectins, C-Type/chemistry , Mannose-Binding Lectins/chemistry , Polymers/chemical synthesis , Polymers/chemistry , Protein Binding , Receptors, Cell Surface/chemistry , Surface Plasmon ResonanceABSTRACT
The glucose oxidase and glucose mediated formation of amphipilic copolymers of N-(ferrocenoylmethyl)acrylamide (NFMA) and N,N-diethylacrylamide (DEA) in aqueous cyclodextrin solution is presented. Thereby, NFMA is not only a comonomer but also part of the redox initiation system. The obtained copolymers contain NFMA units between 1 and 10 mol%. The molecular masses of the copolymers are dependent on the ferrocene content, whereupon molecular weights between 38,000 and 71,000 g mol(-1) are achieved.