Disulfide bridges intermolecular

For the synthesis of double-stranded symmetrical and unsymmetrical monocystine peptides the formation of an intermolecular disulfide bridge is required. For homodimerization of cysteine peptides all the methods discussed in Section 6.1.1 can be applied taking into account the reactivity of the different oxidative agents toward sensitive amino acid residues present in the peptide sequences. Synthetic approaches based on the direct use of suitable cystine derivatives can be envisaged, at least for small-size peptides since disproportionation would in all cases retain the homodimeric structure 241... 

A further development of the DMSO/H+ method for oxidation of cysteine peptides led to the cysteine-sulfoxide acid-catalyzed intermolecular disulfide formation with a second S-unprotected or acid-labile protected cysteine component as shown in Scheme 19. 1471 The protonation of the sulfoxide by TfOH in the case of 5(0)-Mob or TFA in the case of 5(0)-Acm derivatives provides electrophilicity to the sulfur atom to allow attack by the second S-unprotected cysteine component (formed by the fast deprotection of the 5-Mob group with TfOH in presence of dimethylsulfide) to generate in a site-directed manner the interchain disulfide bond. Although extensive experience with this method has not been accumulated for interchain disulfide bridging, it has been successfully applied for intrachain site-directed disulfide bond formation in chicken calcitonin-gene-related peptide.1 79 ... 

Oxidation of mono-cysteine peptides to the dimer is a straightforward reaction that can produce only the desired product. In the case of bis-cysteine peptides statistically the oxidation leads to the homodimers in parallel and antiparallel orientation as well as to the disulfide-bridged monomer and oligomers. When the two cysteine residues are placed in the adjacent position formation of homodimers is highly favored over the cyclic monomer (Section 6.1.5.1) and the product distribution depends strongly on the peptide concentration. Such a type of intermolecular disulfide bridging is present in bovine seminal ribonuclease, where an antiparallel alignment occurs at the interface of the dimer. 97 ... 

The mechanism of regulation of HRI kinase by heme is not well understood. Inactive and active forms of the HRI kinase differ in the content of intermolecular disulfide bridges of the HRI kinase dimer. However it is still imclear how heme targets the kinase and whether the disulfide bridges directly influence the kinase activity. 

One may stress that in proteins clefts are built by coiling back and forth a linear thread maintained by intermolecular binding forces (and eventually a few disulfide bridges). In the case of smaller synthetic molecules, organic synthesis provides means for building the molecular architecture using more highly connected cornerstones. 

Two polypeptide chains are cross linked by intermolecular disulfide bridges. 

Fig. 5. Schematic representation of the collagen IV molecule, which consists of two al(IV) chains and one a2(IV) chain. The non-triple-helical interruptions of the triple helix are indicated by black bars. The cysteine residues (C) and lysine or hydroxylysine (K) residues putatively involved in intra- or intermolecular bonds are shown. CHO designates a N-giycosidically bound oligosaccharide chain. The subscript numerals indicate the number of residues in a distinct region, summarized for all three a-chains. P designates a main pepsin cleavage site. In interruption 13, the a2(IV) chain forms a 21-residue-long loop, stabilized by an interchain disulfide bridge. NCI, Noncollagenous domain 1 TH, triple-helical domain 7 S, carboxyl-terminal domain.

Kato, Y., Oozawa, E., Matsuda, T. 2001. Decrease in antigenic and allergenic potentials of ovomucoid by heating in the presence of wheat flour Dependence on wheat variety and intermolecular disulfide bridges. J Agric Food Chem 49 3661-3665. 

Oxidation of sulfhydryl groups leads to formation of intra- and intermolecular disulfide bridges but may also go further, with formation of sulfoxides and sulfones... 

SODl. In fact, in the crystallographic analysis of CCS-SODl heterodimer, domain III is closely juxtaposed to the active site of SODl. Interestingly, one of the CCS CXC cysteines forms an intermolecular disulfide bridge with an essential cysteine in SODl, perhaps representing an intermediate in the copper transfer process. ... 

Similarly, human fibroblast interferon p contains three cysteines at positions 17, 31, and 141. Of these, cysteines at positions 31 and 141 appear to be involved in a disulfide bridge, and are required for antiviral activity of the molecule. Replacement of the free cysteine residue at position 17 with serine resulted in a 10-fold increase in the specific activity of interferon p expressed and purified from E. coU, which also showed improved stability during storage. These improvements are attributed to elimination of intermolecular aggregation and incorrect disulfide bonds caused by the free cysteine 17 (Mark et al, 1984). 

ADP-Glc PPase from potato tuber has an intermolecular disulfide bridge that links the two small subunits by the Cys residue it can be activated by reduction of the Cys disul-hde linkage (46). At low concentrations (lOjxM) of 3-PGA, both spinach leaf reduced thioredoxin/ and m reduce and activate the enzyme. Fifty percent activation was observed for 4.5-and 8.7- xM reduced thioredoxin/ and m (47). The activation was reversed by oxidized thioredoxin. Cys is conserved in the ADP-Glc PPases from plant leaves and other tissues except for the monocot endosperm enzymes. In photosynthetic tissues, this reduction may also be physiologically pertinent in the hne regulation of the ADP-Glc PPase. 

Selective Reduction of the Intermolecular Disulfide Bridge in Human Glial Cell Line-Derived Neurotrophic Factor Using Tris-(2-Carboxyethyl)Phosphine... 

It was originally suggested that the links between the basic units are through intermolecular disulfide bridging between cysteine residues in the naked end r ons. Reduction of mucins by thiols produced the M, 500,000 forms (see, for example. Refs. 26 and 36). However, Creeth observed a variety of forms in the 0.5-2.0 X 10 r on, and subsequent observations on cervical and other mucins by Carlstedt and Sheehan S yielded, in the presence of guanidine hydrochloride (Gu-HQ), species having forms M, 2 X 10 which they referred to as... 

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