Peptides disulfide bridges

Disulfide bridge (Section 27 7) An S—S bond between the sulfur atoms of two cysteine residues in a peptide or pro tein... 

Biological function and chemistry of endothelin, vasoactive peptide with macro-cyclic fragments formed by disulfide bridges between cysteine residues 99CCC1211. 

These steps can be repeated to add one amino acid at a time to the growing chain or to link two peptide chains together. Many remarkable achievements in peptide synthesis have been reported, including a complete synthesis of human insulin. Insulin is composed of two chains totaling 51 amino acids linked by two disulfide bridges. Its structure was determined by Frederick Sanger, who received the 1958 Nobel Prize in chemistry for his work. 

The primary structure - the sequence of peptide-bonded amino acids in the protein chain and the location of any disulfide bridges. 

Bachinger, H.P., Bruckner, P., Timpl, R., Prockop, D.J. and Engel, J. (1980) Folding mechanism of the triple helix in type-III collagen and type-III pN-collagen role of disulfide bridges and peptide bond isomerisation. European Journal of... 

Momany, F. A., R. Rone, H. Kunz, R. F. Frey, S. Q. Newton, and L. Schafer. 1993. Geometry Optimization, Energetics and Solvation Studies on Four- and Five-mem-bered Cyclic and Disulfide-bridged Peptides, Using the Programs QUANTA3.3 and CHARMm 22. J. Mol. Struct. 286, 1-18. 

Finally, special mention must be made of Cys, which, when present alone, can be considered to belong to the polar uncharged group described above. It can, however, when correctly positioned within the three-dimensional (3-D) structure of a protein, form disulfide bridges with another Cys residue (Figure 4.2). These are the only covalent bonds, apart from the peptide bond of course, that we usually find in proteins2. 

Depending on the structure calculation program used, special covalent bonds such as disulfide bridges or cyclic peptide bonds have to be enforced by distance constraints. Disulfide bridges may be fixed by restraining the distance between the two sulfur atoms to 2.0-2.1 A and the two distances between the Cb and the sulfur atoms of different residues to 3.0-3.1 A [7]. 

The A and B peptide chains in insulin are linked through disulfide bridges. Their presence was suspected from the change in molecular weight which followed the reduction of insulin. For quantitative analyses the S-S bridges had to be broken. Sanger, following the approach used by Toennies and Homiller (1942), oxidized the protein with performic acid, so that the half-cystines were converted to cysteic acid. After oxidation, insulin could be separated into its A and B chains, the A peptide with 20 amino acid residues and the B with 30. 

Physiologists had postulated for a long time about the existence of a sodium excreting hormone to prevent Na overload and consequent deleterious effects of high blood pressure on the heart and vascular system. At least two such natriuretic factors have been described atrial or A-type and brain or B-type natriuretic factors. Structurally, the natriuretic factors are peptides with a cysteine-cysteine disulfide bridge creating a characteristic loop , this is illustrated by Figure 8.8. 

The differences in reactivity between the three Asn residues has been explained by their molecular environment [134], AsnA18 appears protected from deamidation by being flanked at the C-terminal side with a bulky Tyr, and by being positioned in an a-helix and close to a disulfide bridge. In contrast, AsnA21 is at the C-terminus of chain A and appears readily accessible for acid catalysis. As for AsnB3, it is located in a flexible part of the peptide sequence and can, thus, react at neutral pH to form the intermediate succinimide (Fig. 6.29, Pathway e). 

Solouki, T. Emmet, M.R. Guan, S. Marshall, A.G. Detection, Number, and Sequence Location of Sulfur-Containing Amino Acids and Disulfide Bridges in Peptides by Ultrahigh-Resolution MALDI-FTICR Mass Spectrometry. Anal. Chem. 1997,69, 1163-1168. 

Marshall, A.G. Detection, Number, and Sequence Location of Sulfur-Containing Amino Acids and Disulfide Bridges in Peptides by Ultrahigh-Resolution... 

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