Trehalose-Rich, Degradable Hydrogels Designed for Trehalose Release under Physiologically Relevant Conditions

Abstract

Trehalose, a natural disaccharide, is primarily known for its ability to protect proteins from inactivation and denaturation caused by a variety of stress conditions. Furthermore, over the past few years, it has emerged as a promising therapeutic candidate for treatment of neurodegenerative diseases. Herein, we examine the attachment of trehalose to polymers for release under selected physiologically relevant conditions. The proposed strategies are evaluated specifically using hydrogels undergoing simultaneous degradation during trehalose release. These materials are fabricated via copolymerization of the appropriate acrylamide-type monomers with polymerizable trehalose esters or benzylidene acetals. This provides trehalose release in a slightly alkaline (i.e., pH 7.4) or mildly acidic (i.e., pH 5.0) environment, respectively. Using this method materials containing up to 51.7 wt% of trehalose are obtained. The presented results provide a solid basis for future studies on polymeric materials intended for trehalose release in biological systems.

Trehalose coated nanocellulose to inhibit the infections by S. aureus

“…Initially, the trehalose acrylate monomer, 6- O -acryloyl- trehalose (Tre-A), was first synthesized based on an established procedure (ESI, Scheme S1†). 27 The aldehyde-functionalized RAFT agent (aldehyde-CTA) was obtained using a modified procedure from literature (Fig. 1b).…”

The Core–Shell Structure, Not Sugar, Drives the Thermal Stabilization of Single-Enzyme Nanoparticles

“…A trehalose monomertrehalose 6-Oacrylate (TreA)was synthetized in a four-step procedure employing the trimethylsilyl (TMS)-protecting group strategy (Scheme S1, Supporting Information). 59 Thanks to the differences in the susceptibility of primary and secondary trimethylsilyl-protected hydroxyl groups for methanolysis, it is possible to isolate a monofunctional product. In contrast to trehalose, sucrose is composed of glucose and fructose subunits and contains three primary hydroxyl groups (OH-6, OH-1′, and OH-6′).…”

“…The RAFT agent 3-(benzylsulfanylthiocarbonyl-sulfanyl)-propionic acid (BSPA) and PEG 43 -based macroRAFT agent poly­(ethylene glycol) 43 -(benzyl sulfanyl thiocarbonyl-sulfanyl)-propionate (PEG 43 -BSPA) was synthesized according to our previous work . Trehalose acrylate (TreA) was synthesized according to a published literature from Malgorzata Milewska (née Burek), and sucrose acylate (SuA) was synthesized in a similar way as described in the Supporting Information.…”

“…After SEN formation, the protective layer was stabilized by cross-linking. With the help of scattering techniques (dynamic light scattering (DLS) and small-angle X-ray scattering 57 Trehalose acrylate (TreA) was synthesized according to a published literature from Malgorzata Milewska (neé Burek), 59 and sucrose acylate (SuA) was synthesized in a similar way as described in the Supporting Information. Synthesis of Diblock Polyelectrolytes: PEG 43 -b-P(DMAPA 52co-AM 30 ) (C-A), PEG 43 -b-P(DMAPA 51 -co-TreA 32 ) (C-T), and PEG 43 -b-P(DMAPA 51 -co-SuA 30 ) (C-S).…”

Structurally analogous trehalose and sucrose glycopolymers – comparative characterization and evaluation of their effects on insulin fibrillation

“…These glycomonomers were synthesized precisely by employing a trimethylsilyl protecting group strategy (Schemes S1 and S2 †) described in our recent reports. 47,48 The details and a short discussion of this synthesis, as well as the relevant 1D and 2D NMR spectra (Fig. S1-S16 †), are given in the ESI.…”