Maleimide End Research Articles

Synthesis and Characterization of a Red-Shifted, Fast Relaxing, Photoswitchable Tethered Ligand for use in Modified Glutamate Receptors

A two-component chemical and biological approach based on a Photoswitchable Tethered Ligand (PTL) and a modified ionotropic glutamate receptor (LiGluR) was recently developed. The PTL Maleimide-Azobenzene-Glutamate (MAG) takes advantage of the photochemistry of azobenzene, which changes its shape depending on the irradiation wavelength used. When MAG covalently binds via its maleimide end to an engineered cysteine residue near the ligand binding domain of LiGluR, it allows for the precise control of channel gating, as light isomerizes the azobenzene and docks or removes the glutamate from the receptor binding site. The photochemical properties of MAG offer opportunity for shifting the activating wavelength from UV light (380 nm), which is scattered by tissue and therefore penetrates poorly. We have synthesized a red-shifted MAG (460 nm peak absorption) and used it on LiGluR in whole-cell patch clamp experiments in HEK293 cells. The red-shifted MAG functions as state-dependent tethered agonist, which can be activated with a broad spectrum of visible light and thermally relaxes to inactivity.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Redox‐Responsive Degradable PEG Cryogels as Potential Cell Scaffolds in Tissue Engineering

A Michael addition strategy involving the reaction between a maleimide double bond and amine groups is investigated for the synthesis of cryogels at subzero temperature. Low-molecular-weight PEG-based building blocks with amine end groups and disulfide-containing building blocks with maleimide end groups are combined to synthesize redox-responsive PEG cryogels. The cryogels exhibit an interconnected macroporous morphology, a high compressive modulus and gelation yields of around 95%. While the cryogels are stable under physiological conditions, complete dissolution of the cryogels into water-soluble products is obtained in the presence of a reducing agent (glutathione) in the medium. Cell seeding experiments and toxicologic analysis demonstrate their potential as scaffolds in tissue engineering.

Reversible polymerization of novel monomers bearing furan and plant oil moieties: a double click exploitation of renewable resources

Monomers based on plant oil derivatives bearing furan heterocycles appended through thiol-ene click chemistry were prepared and, subsequently, polymerized via a second type of click reaction, i.e. the Diels–Alder (DA) polycondensation between furan and maleimide complementary moieties. Two basic approaches were considered for these DA polymerizations, namely (i) the use of monomers with two terminal furan rings in conjunction with bismaleimides (AA + BB systems) and (ii) the use of a protected AB monomer incorporating both furan and maleimide end groups. This study clearly showed that both strategies were successful, albeit with different outcomes, in terms of the nature of the ensuing products. The application of the retro-DA reaction to these polymers confirmed their thermoreversible character, i.e. the clean-cut return to their respective starting monomers, opening the way to original macromolecular materials with interesting applications, like mendability and recyclability.

Synthesis of Semitelechelic Maleimide Poly(PEGA) for Protein Conjugation By RAFT Polymerization

Maleimide end functionalized polymers for site-selective conjugation to free cysteines of proteins were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. A furan-protected maleimide chain transfer agent (CTA) was employed in the RAFT polymerization of poly(ethylene glycol) methyl ether acrylate (PEGA). Gel permeation chromatography (GPC) with laser light scattering detection indicated that 20,000 and 39,000 Da polyPEGA had been made with polydispersity indices of 1.25 and 1.36, respectively. The maleimide group on the polymer chain end was exposed by heating the poly(PEGA)s for 4 h. The deprotection efficiency was estimated to be 80 and 60% for poly(PEGA)(20 kDa) and poly(PEGA)(39 kDa), respectively. Maleimide-poly(PEGA)s were conjugated to V131C T4 lysozyme (T4L), and the resultant polymer-protein conjugates were characterized by size exclusion chromatography and gel electrophoresis.

The Rapid Chain Extension of Anthracene‐Functional Polyesters by the Diels‐Alder Reaction with Bismaleimides

AbstractSummary: The chain extension of anthracene end‐capped oligoesters by reaction with bismaleimides constitutes a rapid route to high molecular weight polyesters. Polytransesterification of bis(2‐hydroxyethyl) terephthalate in the presence of a small amount of 2‐hydroxyethyl 2‐anthracenecarboxylate provides low molecular weight anthracene‐terminated macromers with anthracene end group functionality (fAN) of 1.66–1.85. These are subject to rapid chain extension with di(4‐maleimidophenyl)methane by Diels‐Alder cycloadditions resulting in consumption of the anthracene and maleimide end groups to generate polymers with $\overline M _{\rm n}$ > 2.0 × 104 g · mol−1. Thus, generation of the polymeric structure is achieved rapidly by addition reactions rather than sluggish transesterification reactions in which a condensate must be removed from the viscous polymer melt.Chain extension of low‐molecular weight 2‐anthracenecarboxylate terminated oligoesters.magnified imageChain extension of low‐molecular weight 2‐anthracenecarboxylate terminated oligoesters.

Kinetics of tethering quaternary ammonium compounds to K(+) channels.

Polymeric maleimido–quaternary ammonium (QA) compounds have been shown to function as molecular tape measures when covalently tethered to external cysteine residues of a Shaker K+ channel (Blaustein R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309–311). For sufficiently long compounds, the cysteine–maleimide tethering reaction creates a high concentration, at the channel's pore, of a TEA-like moiety that irreversibly blocks current. This paper investigates a striking feature of the maleimide–cysteine tethering kinetics. Strong blockers—those that induce substantial levels (>80%) of irreversible inhibition of current—react with channel cysteines much more rapidly than weak blockers and, when delivered to channels with four cysteine targets, react with multiexponential kinetics. This behavior is shown to arise from the ability of a strong blocker to concentrate its maleimide end near a channel's cysteine target by exploiting the reversible pore-blocking affinity of its QA headgroup.

Surface modification of diaspirin cross-linked hemoglobin (DCLHb) with chondroitin-4-sulfate derivatives. Part 1.

Synthetic methodology was developed for the preparation of chondrotin-4-sulfate reagents that could be specifically attached to the surface of diaspirin cross-linked hemoglobin (DCLHb), a chemically stabilized human hemoglobin. The surface-modified hemoglobin solutions had a significantly higher colloidal osmotic pressures (COP) than DCLHb. The P(50) of the modified DCLHb was dependent upon the reactive end group of the chondrotin-4-sulfate reagents that was used for the protein modification. Modification of DCLHb with the chondroitin-4-sulfate derivatives containing the maleimide end group 23 provided a hemoglobin with a P(50) value of 23 mmHg, while the P(50) of hemoglobins prepared from chondroitin-4-sulfate derivatives containing the aldehyde end group 13 and 18 remained unchanged from that of DCLHb.

A novel reactive liquid rubber with maleimide end groups for the toughening of unsaturated polyester resins

An amino-terminated butadiene–acrylonitrile copolymer was chemically modified into a maleim-ido-terminated rubber and was used as a toughening agent for an unsaturated polyester resin. The reactive rubber was characterized by Fourier transform infrared spectroscopy. The mechanical and fracture properties of the blends containing the unmodified and the modified rubbers were investigated. Furthermore, a morphological analysis was carried out by scanning and transmission electron microscopy. A substantial enhancement of toughness was found when the modified rubber was used in place of the plain copolymer. © 1996 John Wiley & Sons, Inc.

A novel reactive liquid rubber with maleimide end groups for the toughening of unsaturated polyester resins

An amino-terminated butadiene–acrylonitrile copolymer was chemically modified into a maleim-ido-terminated rubber and was used as a toughening agent for an unsaturated polyester resin. The reactive rubber was characterized by Fourier transform infrared spectroscopy. The mechanical and fracture properties of the blends containing the unmodified and the modified rubbers were investigated. Furthermore, a morphological analysis was carried out by scanning and transmission electron microscopy. A substantial enhancement of toughness was found when the modified rubber was used in place of the plain copolymer. © 1996 John Wiley & Sons, Inc.

The crosslinking of eutectic mixtures of bismaleimides

The high reactivity of the maleimide groups in bismaleimide resins is attributable to the electron withdrawing effect of the carbonyl groups causing the carbon carbon double bonds to become electron deficient. Consequently, bismaleimides homopolymerize readily to form network polymers without the aid of catalyst at temperatures between 150 and 300°. This paper is concerned with the effect on the reaction rate of the bridging group between the maleimide end groups. Observations of the crosslinking of a eutectic mixture of three oligomers containing different bridging groups suggest that the reactivity is similar for all three. Nevertheless when one of the three oligomers was crosslinked by itself, it reacted much more rapidly than the mixture. These observations are believed to reflect the steric hindrance effect of one or both of the other bismaleimide oligomers on the rate of reaction of the eutectic. Similar observations were found with rubber-toughened bismaleimide systems. The probability of steric hindrance from the aliphatic and the aromatic oligomers is discussed.

Elastomeric behaviour of crosslinked poly(aryl ether ketone)s at elevated temperatures

A new approach to thermally stable elastomers for use between temperatures of 180°C and 275°C has been developed. Wholly aromatic poly(aryl ether ketone)s of various molecular weights have been synthesized with maleimide end groups. These structures have glass transition temperatures ( T gs) in the 150°C range, and when thermally crosslinked, they exhibited elastomeric characteristics ∼30–50°C above their T gs (∼200°C). The moduli of the networks at 200°C were comparable to those of unreinforced poly(dimethylsiloxane) elastomers (1–2 MPa) and the elongations ranged from 200 to 300%. The poly(aryl ether ketone) elastomers showed exceptional thermal stability with little weight loss up to 490°C. The results from the chemorheology and stress relaxation measurements are discussed and compared to poly(dimethylsiloxane) networks.