Disulfide cross-links, reduction

The chemistry of the reactions of permanent waves with human hair involves reduction of disulfide cross-links and molecular shifting by stressing the hair on rollers followed by reoxidation. These reactions produce extensive changes to the tensile properties of the fibers, both during reduction and even after reoxidation. 

Reagents containing thiol groups, usually mercaptoethanol or thioglycolic acid, are used to reduce the disulfide cross-links in wool [13,242]. Tributyl phosphine and sulfites are also used. Normally, reduction of wool affects only cystine residues no other amino acid side-chains react. 

Clothes-moth [13,175,269,270] larvae attack wool with a mixture of enzymes that catalyze the reduction of cystine residue disulfide cross-links and the hydrolysis of peptide bonds. Wool is usually moth-proofed by treatment with insecticides that are absorbed like dyes and show similar fastness. The wool textile industry applies insect-resistant agents mainly to carpet wools, which account for about 85% of the treated wool. Insect-resistant agents are of two classes those which have been developed specifically for use on wool, and those which consist of agricultural insecticides that have been specially formulated for use with wool. The former group is usually polychlorinated aromatic compounds, and the latter group is based on synthetic pyrethroid insecticides. 

Breaking the disulfide cross-links in a wool fiber by oxidation, or by reduction and alkylation, makes it easier to extend. 

Reduction-responsive DDS have also been proven valuable for the delivery of proteins in the cytosol. In recent work, caspase 3 was encapsulated in a thin, positively charged polymer shell interconnected by disulfide cross-links. The redox-responsive nanocapsules formed in this way were able to induce apoptosis in several human cancer cell lines, owing to efficient cellular uptake and protein release in the reductive cytosol (Zhao et al, 2011). 

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

Bifunctional reagents, such as bis-imido esters, have been widely used because they react under mild condidons specifically with the amino groups of proteins. Bifunctional imido esters that introduce a disulfide bond in the cross-link are especially useful since these bonds can be readily cleaved by reduction, allowing individual proteins to be regenerated. The reagent most commonly used for ribosomal proteins is 2-iminothiolane (Traut et al, 1980). 

Similar keratin filaments are found in hair. In a single wool fiber with a diameter of about 20 pm, millions of filaments are bundled together within dead cells. The individual keratin helices are cross-linked and stabilized by numerous disulfide bonds (see p. 72). This fact is exploited in the perming of hair. Initially, the disulfide bonds of hair keratin are disrupted by reduction with thiol compounds (see p. 8). The hair is then styled in the desired shape and heat-dried. In the process, new disulfide bonds are formed by oxidation, which maintain the hairstyle for some time. 

Kim et al. used the exchange reaction to synthesize cross-linked AuNP-PNIPAM core-shell hybrid structures, as well as a brush-type AuNP/PNIPAM hybrid through surface-initiated ATRP in an aqueous medium. The disulfide initiators, [BrC (CH3)2COO(CH2)iiS]2, were bound to AuNPs synthesized by citrate reduction. They have studied the effect of cross-linking on the thermo-responsiveness of the AuN / PNIPAM hybrids for potential use as a stimuli responsive optical device, such as surface plasmon resonance-based sensing materials [91]. 

Figure 123 The reaction of DSP with amine-containing molecules yields amide bond cross-links. The conjugates may be cleaved by reduction of the disulfide bond in the cross-bridge with DTT.

Figure 124 DTSSP can form cross-links between two amine-containing molecules through amide linkages. The conjugates may be cleaved by disulfide reduction using DTT.

Figure 157 SMPT can form cross-links between an amine-containing molecule and a sulfhydryl-containing compound through amide and disulfide linkages, respectively. The hindered nature of the disulfide group provides better stability toward reduction and cleavage.

Figure 177 SAND can be used to modify amine-containing molecules, and then photoinitiate cross-linking to another amine-containing molecule via a ring-expansion process. The conjugates may be disrupted by reduction of the cross-bridge disulfide with DTT.

Figure 181 SAED may be used to transfer the fluorescent AMCA label from the first molecule modified with the cross-linker to the second molecule cross-linked with it by reduction of its internal disulfide bond with DTT. Thus, unknown target molecules may be fluorescently tagged to follow them in vivo.

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