Design cross-linker

Coiled coils are interesting as designable cross-linkers because of the well-understood relation between the peptide sequence, the folded and dimerized structure, and the binding affinity. However, as described above, hydrogels based on coiled coils are generally weak, with shear moduli only up to 1 kPa. Furthermore, the use of recombinant protein expression or solid-phase peptide synthesis limits the scale on which these materials can be prepared. However, this approach allows tuning both the cross-Unks as well as the backbone to regulate the mechanical properties and incorporate bioactivity. 

Fig. 9. A de novo designed P sheet protein, betabellin, formed by the dimerization of two identical four-stranded -sheets and a disulfide linking the two sheets. This model is for betabeUins 9 and later progenies the earher betabeUins contained a two-armed cross-linker connecting the sheets (51).

Fig. 10. Generalized formulation design outline for radiation-curable coatings and adhesive systems. The cross-linker is a multifimctional unsaturated cross-linking agent or oligomer, rj = viscosity CR = cure rate S = shrinl ge H = hardness F = flexibility A = adhesion 7 = surface energy ...

Soften and render products more flexible by reduction of the brittleness of the end-product. Also used to modify viscosity and improve the flow characteristics and processability of a polymer. Are designed to space out the polymer molecules, facilitating their movements and leading to enhanced flexibility (lower modulus) and ductility. Plasticisers may play a dual role as stabilisers or cross-linkers. Performance criteria are compatibility, plasticising efficiency, processability and permanence. 

Kushner AM, Gabuchian V, Johnson EG, Guan Z. Biomimetic design of reversibly unfolding modular cross-linker to enhance mechanical properties of 3D network polymers. J Am Chem Soc 2007 129 14110. 

The differences within these families of reagents generally relate to the length of the spacer or bridging portion of the molecule. Occasionally, the bridging portion itself is designed to be cleavable by one of a number of methods (Chapter 7). The great majority of homobifunctional, sulfhydryl-reactive cross-linkers mentioned in the literature are not readily available from commercial sources and would have to be synthesized to make use of them. The ones listed in this section are obtainable from Pierce Chemical. 

The number of commercially available cross-linkers for sulfhydryl- and photoreactive conjugations provide enough variety to design successful experiments in photolabeling active centers and studying macromolecular interactions. 

Figure 195 Cross-linkers containing a diol group in their cross-bridge design may be cleaved by oxidation with sodium periodate.

Figure 315 The basic design of an immunotoxin conjugate consists of an antibody targeting component cross-linked to a toxin molecule. The complexation typically includes a disulfide bond between the antibody portion and the cytotoxic component of the conjugate to allow release of the toxin intracellularly. In this illustration, an intact A—B toxin protein provides the requisite disulfide, but the linkage also may be designed into the cross-linker itself.

Fig. 3 Application of the Doehlert experimental design to optimize a MIP for propranolol with respect to the type of cross-linker (EDMA or TRIM) and the degree of cross-linking, (a) Three-dimensional representation of response surfaces for the percentage of bound [3H]propanolol to the molecularly imprinted polymer (MIP) and the corresponding non-imprinted control polymer (NIP), (b) Contour plot of the function describing binding of [3H]propanolol to MIPs relative to the degree and the kind (bi or trifunctional) cross-linking. The values were corrected for non-specific binding to the non-imprinted control polymer. Adapted from [31] with kind permission from Springer Science + Business Media...

Recently, a parathion-selective voltammetric MIP chemosensor was designed [205]. The parathion-imprinted polymer particles were prepared by polymerization of an MAA functional monomer, EGDMA cross-linker and AIBN initiator. Subsequently, the powdered MIP particles were blended with a graphite powder, in the presence of n-icosane. to form an (MlP)-(carbon paste) (MIP-CP) electrode. After removal of the template, MIP-CP much more selectively rebound parathion than the (non-imprinted imprinted polymer)-(carbon paste) carbon paste (NIP-CP) electrode. Recognition ability of the MIP-CP electrode was very high compared to that of the NIP-CP electrode. The chemosensor response was calibrated in the linear range of 1.7-900 nM parathion and LOD was 0.5 nM [205]. This chemosensor selectively determined parathion in the presence of its structural and functional counterparts, such as paraxon, in real samples. 

DVB were valid in this system as well. These concern the dependence of surface area and pore volume on the amount of diluent and cross-linker. The surface area increases with the amount of EDMA and goes through a maximum with increasing amount of diluent. Using cyclohexanol-dodecanol as a solvent-non-solvent pair, the factors of importance for the structure and morphology of the polymers were studied by experimental design [34]. In these experiments the concentration of the diluent mixture was varied between 20 and 77% (volume/total volume), the concentration of EDMA between 25 and 100% (volume/monomer volume), the concentration of initiator (AIBN) between 0.2 and 4% (w/w), the concentration of non-solvent (dodecanol), between 0 and 15% (v/v) and the polymerisation temperature between 70° and 90°C. The surface area (determined by nitrogen sorption), pore volume (determined by mercury porosimetry) (see Section 2.11.6.) and the mechanical properties were chosen as responses. 

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