Electron Delocalization Through the Disulfide Bridge

[1-β-Mercaptopropionic acid, 8-norarginine]vasopressin (L8, D8; I, II) was prepared by condensation of β-benzylthiopropionyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteine with Nγ-benzyloxycarbonyl-α,γ-diaminobutyryl-glycine amide (L2, D2) by the azide or carbodiimide method, respectively, removal of the benzyloxycarbonyl residue, guanidination of γ-amino groups, removal of protecting groups, closing of the disulfide bridge, and electrophoretic purification. I has an almost 2 times higher antidiuretic effect than DDAVP and a 3 times higher pressor effect than AVP. II has 20-25% of the antidiuretic effect of DDAVP and 16 IU/mg of the pressor effect.

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Synthesis and pharmacological properties of oxytocin analogues modified simultaneously in position 2 and in the disulfide bridge

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19802855 ◽

1980 ◽

Vol 45 (10) ◽

pp. 2855-2864 ◽

Cited By ~ 3

Author(s):

Michal Lebl ◽

Tomislav Barth ◽

Karel Jošt

Keyword(s):

Biological Activities ◽

Disulfide Bridge ◽

Pharmacological Properties

Analogues of deamino-6-carba-oxytocin, containing isoleucine, O-methyltyrosine or methionine in position 2, either in the sulfide or sulfoxide form, were prepared and studied pharmacologically. These compounds had considerably lower biological activities than the analogous compounds of the 1-carba series. Furthermore, analogues of [1,6-homolanthionine]deamino-oxytocin were prepared with O-methyltyrosine or isoleucine in position 2; these compounds had a certain degree of oxytocic activity.

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Carbo-[3]oxocarbon and its isomers: evaluation of the stability and of the electron delocalization

Physical Chemistry Chemical Physics ◽

10.1039/b718817j ◽

2008 ◽

Vol 10 (24) ◽

pp. 3578 ◽

Cited By ~ 4

Author(s):

Mickaël Gicquel ◽

Jean-Louis Heully ◽

Christine Lepetit ◽

Remi Chauvin

Keyword(s):

Electron Delocalization ◽

The Stability

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Influence of pH, Temperature and Protease Inhibitors on Kinetics and Mechanism of Thermally Induced Aggregation of Potato Proteins

Foods ◽

10.3390/foods10040796 ◽

2021 ◽

Vol 10 (4) ◽

pp. 796

Author(s):

David J. Andlinger ◽

Pauline Röscheisen ◽

Claudia Hengst ◽

Ulrich Kulozik

Keyword(s):

Protein Interactions ◽

Disulfide Bonds ◽

Food Systems ◽

Disulfide Bridge ◽

Food Protein ◽

Potato Protein ◽

Covalent Bonds ◽

Bridge Formation ◽

Induced Aggregation ◽

Influence Of Ph

Understanding aggregation in food protein systems is essential to control processes ranging from the stabilization of colloidal dispersions to the formation of macroscopic gels. Patatin rich potato protein isolates (PPI) have promising techno-functionality as alternatives to established proteins from egg white or milk. In this work, the influence of pH and temperature on the kinetics of PPI denaturation and aggregation was investigated as an option for targeted functionalization. At a slightly acidic pH, rates of denaturation and aggregation of the globular patatin in PPI were fast. These aggregates were shown to possess a low amount of disulfide bonds and a high amount of exposed hydrophobic amino acids (S0). Gradually increasing the pH slowed down the rate of denaturation and aggregation and alkaline pH levels led to an increased formation of disulfide bonds within these aggregates, whereas S0 was reduced. Aggregation below denaturation temperature (Td) favored aggregation driven by disulfide bridge formation. Aggregation above Td led to fast unfolding, and initial aggregation was less determined by disulfide bridge formation. Inter-molecular disulfide formation occurred during extended heating times. Blocking different protein interactions revealed that the formation of disulfide bond linked aggregation is preceded by the formation of non-covalent bonds. Overall, the results help to control the kinetics, morphology, and interactions of potato protein aggregation for potential applications in food systems.

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The Role of the Disulfide Bridge in the Copper (II) Binding by the Cyclic His4-Peptide

International Journal of Molecular Sciences ◽

10.3390/ijms22126458 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6458

Author(s):

Aleksandra Pieniężna ◽

Weronika Witak ◽

Aneta Szymańska ◽

Justyna Brasuń

Keyword(s):

Metal Ions ◽

Coordination Mode ◽

Transition Metal Ions ◽

Disulfide Bridge ◽

Chain Flexibility ◽

Vis Spectroscopy ◽

Ph Range ◽

Cd Studies ◽

Metal Ratios

In this paper, we present studies on the influence of the disulfide bridge on the copper (II) ions’ binding abilities by the cyclic His4-peptide. The studied ligand HKHPHRHC-S-S-C consists of nine amino acids. The cyclic structure was obtained through a disulfide bridge between two cysteinyl groups. Moreover, this peptide is characterized by the presence of four His residues in the sequence, which makes it an interesting ligand for transition metal ions. The potentiometric and spectroscopic (UV-Vis spectroscopy and circular dichroism spectroscopy (CD)) studies were carried out in various molar ligand to metal ratios: 2:1, 1:1, and 1:2, in the pH range of 2.5–11 at 25 °C. The results showed that the cyclic His4-peptide promotes dinuclear complexes in each of these systems and forms the final dinuclear species with the {NIm, 3N-amide}{NIm, 3N-amide} coordination mode. The obtained data shows that cyclization by the formation of the disulfide bond has an impact on the peptide chain flexibility and appearance of additional potential donors for metal ions and influences the copper (II) ions’ coordination.

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Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin

Biological Chemistry ◽

10.1515/bc.2004.151 ◽

2004 ◽

Vol 385 (12) ◽

pp. 1171-1175 ◽

Cited By ~ 7

Author(s):

Zhan-Yun Guo ◽

Xiao-Yuan Jia ◽

You-Min Feng

Keyword(s):

Biological Activity ◽

Disulfide Bonds ◽

Negative Charge ◽

Disulfide Bridge ◽

Site Directed Mutagenesis ◽

Side Chain ◽

Insulin Analogs ◽

High Biological Activity ◽

Chemical Groups ◽

Structure And Activity

Abstract Insulin contains three disulfide bonds, one intrachain bond, A6–A11, and two interchain bonds, A7–B7 and A20–B19. Site-directed mutagenesis results (the two cysteine residues of disulfide A7–B7 were replaced by serine) showed that disulfide A7–B7 is crucial to both the structure and activity of insulin. However, chemical modification results showed that the insulin analogs still retained relatively high biological activity when A7Cys and B7Cys were modified by chemical groups with a negative charge. Did the negative charge of the modification groups restore the loss of activity and/or the disturbance of structure of these insulin analogs caused by deletion of disulfide A7–B7? To answer this question, an insulin analog with both A7Cys and B7Cys replaced by Glu, which has a long side-chain and a negative charge, was prepared by protein engineering, and its structure and activity were analyzed. Both the structure and activity of the present analog are very similar to that of the mutant with disulfide A7–B7 replaced by Ser, but significantly different from that of wild-type insulin. The present results suggest that removal of disulfide A7–B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge.

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