Oxytocin disulfide bridge

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

Oxytocin is a cyclic compound containing a disulfide bridge between two cysteine residues. 

The three-dimensional structure of oxytocin. The sulfur atoms of the disulfide bridge are in yellow. The ... 

By comparing time-resolved and steady-state fluorescence parameters, Ross et alm> have shown that in oxytocin, a lactation and uterine contraction hormone in mammals, the internal disulfide bridge quenches the fluorescence of the single tyrosine by a static mechanism. The quenching complex was attributed to an interaction between one C — tyrosine rotamer and the disulfide bond. Swadesh et al.(()<>> have studied the dithiothreitol quenching of the six tyrosine residues in ribonuclease A. They carefully examined the steady-state criteria that are useful for distinguishing pure static from pure dynamic quenching by consideration of the Smoluchowski equation(70) for the diffusion-controlled bimolecular rate constant k0,... 

In heterodetic peptides, the ring system is formed from amides and other heteroatom linkages, for example, a disulfide bridge, a thioether or a lactone linkage. The most common nonamide links in heterodetic peptides are the disulfide bonds (found in posterior pituitary hormones such as oxytocin and vasopressin) and the ester (lactone) fnnction. " ... 

Oxytocin (OT) is a nonapeptide in which six amino acids form a ring closed by a disulfide bridge, while the ring itself forms an antiparallel pleated sheet. The tail portion of the peptide, composed of Pro-Leu-Gly-NHj, is also rigidly held in a folded conformation. Oxytocin causes the powerful contraction of some smooth muscles and plays a vital role in milk ejection (not to be confused with milk secretion, which is regulated by prolactin). It also has uterotonic action, contracting the muscles of the uterus, and is therefore used clinically to induce childbirth. 

Two cysteine residues may form a disulfide bridge within a single peptide chain, making a ring. Figure 24-9 shows the structure of human oxytocin, a peptide hormone that causes contraction of uterine smooth muscle and induces labor. Oxytocin is a nonapeptide with two cysteine residues (at positions 1 and 6) linking part of the molecule... 

Figure 24-14 shows the first two steps in the sequencing of oxytocin. Before sequencing, the oxytocin sample is treated with peroxyformic acid to convert the disulfide bridge to cysteic acid residues. 

The two Cys residues in oxytocin may be involved in disulfide bridges, either linking two of these peptide units or forming a ring. By measuring the molecular weight of oxytocin, we can show that it contains just one of these peptide units therefore, the Cys residues must link the molecule in a ring. 

When the disulfide bridge is reduced, oxytocin has the constitution Asn, Cysa, Gin, Gly, He, Leu, Pro, T3rr. 

There are examples of proteins with a large number of disulfide bridges, where the relative importance of the covalent link to tertiary structure is more significant. Disulfide links are also more significant in small polypeptides such as the peptide hormones vasopressin (Fig. 3.12) and oxytocin (Fig. 3.13). However, in the majority of proteins, disulfide links play a minor role in controlling tertiary structure. 

Again utilizing the NMR characterization of the /S-turn, the secondary structure of deamino oxytocin has been determined in DMSO-rfj-methanol to be the /3-type conformation indicated in Fig. 4. The handedness of the disulfide bridge is assumed to be the same in DMSO-methanol as in the aqueous system where the optical rotation studies were carried out. ... 

Disulfide bridging. Cysteine units in peptides can be linked by reaction with NIS. Applications of this method in the synthesis of (Arg )-vasopressin, oxytocin, and apamin have been demonstrated. 

The triplet lifetimes at 77 °K of proteins showing an oxytocin-t5q)e phosphorescence are in the range of 1.4—1.7 sec 28b,i49) similar to the value 1.7 sec found from oxytocin m), whereas the lifetime of the tyrosine zwitterion itself is —2.9 sec Xhe phosphorescence lifetime of the dipeptide dimer cystinyl-bis-tyrosine also is 1.7 sec 28b) in contrast with the 2.6 sec lifetime found for the reduced dipeptide cysteinyl-tyrosine Thus, the shortened lifetime is due to the neighboring disulfide linkages and accordingly when the disulfide bridges are reduced the observed protein or peptide hfetimes are found to increase 28b), The ribonuclease A phosphorescence is reported to decay as two first order processes at 77 °K with decay lifetimes of 0.5 sec and 1.6 sec 30). The reduced t T osine phosphorescence lifetime may involve electron transfer to disulfide from the triplet ns). 

The posterior lobe of the pituitary gland, the neurohypophysis, generally secretes two hormones of a family of nine found interspecifically. The same hormones are usually found in a zoological class, and the structure varies by only one or two residues among classes. These neurohypophyseal hormones are nonapeptides with a 1,6-disulfide bridge. In humans these hormones are oxytocin, which plays a role in lactation and parturition by causing smooth muscle contraction, and vasopressin, which has a homeostatic role in controlling water balance. 

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