The problem of disulfide bonds within peptides

Disulfide bonds are an indispensable part of the three-dimensional structure of many proteins. These covalent bonds can be found in almost all extracellular peptides and protein molecules.

A disulfide bond is formed when a cysteine sulfur atom forms a covalent single bond with the other half of the cystine sulfur atom at different positions in the protein. These bonds help stabilize proteins, especially those secreted from cells.

The efficient formation of disulfide bonds involves several aspects such as proper management of cysteines, protection of amino acid residues, removal methods of protective groups, and pairing methods.

Peptides were grafted with disulfide bonds

Gutuo organism has a mature disulfide bond ring technology. If the peptide contains only one pair of Cys, the disulfide bond formation is straightforward. Peptides are synthesized in solid or liquid phases,

It was then oxidized in a pH8-9 solution. The synthesis is relatively complex when two or more pairs of disulfide bonds need to be formed. Although disulfide bond formation is usually completed late in the synthetic scheme, sometimes the introduction of preformed disulfides is advantageous for linking or elongating peptide chains. Bzl is a Cys protecting group, Meb, Mob, tBu, Trt, Tmob, TMTr, Acm, Npys, etc., widely used in symbiont. We specialize in disulphide peptide synthesis including:

1. Two pairs of disulfide bonds are formed within the molecule and two pairs of disulfide bonds are formed between the molecules

2. Three pairs of disulfide bonds are formed within the molecule and three pairs of disulfide bonds are formed between the molecules

3. Insulin polypeptide synthesis, where two pairs of disulfide bonds are formed between different peptide sequences

4. Synthesis of three pairs of disulfide-bonded peptides

Why is cysteinyl amino group (Cys) so special?

The side chain of Cys has a very active reactive group. The hydrogen atoms in this group are easily replaced by free radicals and other groups, and thus can easily form covalent bonds with other molecules.

Disulfide bonds are an important part of the 3D structure of many proteins. Disulphide bridge bonds can reduce the elasticity of the peptide, increase the stiffness, and reduce the number of potential images. This image limitation is essential for biological activity and structural stability. Its replacement may be dramatic for the overall structure of the protein. Hydrophobic amino acids such as Dew, Ile, Val are a helix stabilizer. Because it stabilizes the disulfide-bond α-helix of cysteine formation even if cysteine does not form disulfide bonds. That is, if all cysteine residues were in the reduced state, (-SH, carrying free sulfhydryl groups), a high percentage of helical fragments would be possible.

The disulfide bonds formed by cysteine are durable to the stability of the tertiary structure. In most cases, S-S Bridges between bonds are necessary for the formation of quaternary structures. Sometimes the cysteine residues that form disulfide bonds are far apart in the primary structure. The topology of disulfide bonds is the basis for the analysis of protein primary structure homology. The cysteine residues of the homologous proteins are very conserved. Only tryptophan was statistically more conserved than cysteine.

The cysteine is located in the center of the catalytic site of the thiolase. Cysteine can form acyl intermediates directly with the substrate. The reduced form acts as a "sulfur buffer" that keeps the cysteine in the protein in the reduced state. When the pH is low, the equilibrium favors the reduced -SH form, whereas in alkaline environments -SH is more prone to be oxidized to form -SR, and R is anything but a hydrogen atom.

Cysteine can also react with hydrogen peroxide and organic peroxides as a detoxicant.


Post time: May-19-2023