Comparative evaluation of different methods for disulfide bond formation in synthesis of the HIV‐2 antigenic determinant

Kudryavtseva, Е. V.; Сидорова, М В; Овчинников, М. В.; Bespalova, Zh. D.; Бушуев, В. Н.

doi:10.1111/j.1399-3011.1997.tb01120.x

Cited by 31 publications

(11 citation statements)

References 5 publications

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“…To help limit these, excess iodine should be quenched or adsorbed as quickly as possible after completion of the disulfide bond formation by addition of sodium bisulfite [9], sodium thiosulfate [10], ascorbic acid [11], powdered zinc dust, activated charcoal [12], or by dilution with water followed by extraction with carbon tetrachloride [13]. However, the quenching reagents themselves can sometimes cause additional side reactions including formation of thiosulfate adduct of the peptide [11].…”

Section: Introductionmentioning

confidence: 99%

Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation

Reddy

Kumari

Mallikharjunasarma

et al. 2012

International Journal of Peptides

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The S-acetamidomethyl (Acm) or trityl (Trt) protecting groups are widely used in the chemical synthesis of peptides that contain one or more disulfide bonds. Treatment of peptides containing S-Acm protecting group with iodine results in simultaneous removal of the sulfhydryl protecting group and disulfide formation. However, the excess iodine needs to be quenched or adsorbed as quickly as possible after completion of the disulfide bond formation in order to minimize side reactions that are often associated with the iodination step. We report here a simple method for simultaneous quenching and removal of iodine and isolation of disulphide bridge peptides. The use of excess inexpensive anion exchange resin to the oxidized peptide from the aqueous acetic acid/methanol solution affords quantitative removal of iodine and other color impurities. This improves the resin life time of expensive chromatography media that is used in preparative HPLC column during the purification of peptide using preparative HPLC. Further, it is very useful for the conversion of TFA salt to acetate in situ. It was successfully applied commercially, to the large scale synthesis of various peptides including Desmopressin, Oxytocin, and Octreotide. This new approach offers significant advantages such as more simple utility, minimal side reactions, large scale synthesis of peptide drugs, and greater cost effectiveness.

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Section: Introductionmentioning

confidence: 99%

Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation

Reddy

Kumari

Mallikharjunasarma

et al. 2012

International Journal of Peptides

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“…Several strategies have been included for peptide disulfide bridge arrangement, including the use of orthogonally protected cysteine residues and/or oxidation reactions promoted by reagents such as iodine, thallium trifluoroacetate, potassium ferricyanide, or dimethylsulphoxide [ 45 , 46 , 47 , 48 ]. However, strong oxidant compounds can also affect other amino acid residues, like tryptophan and tyrosine [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Chemical Synthesis and Functional Analysis of VarvA Cyclotide

et al. 2018

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Cyclotides are circular peptides found in various plant families. A cyclized backbone, together with multiple disulfide bonds, confers the peptides’ exceptional stability against protease digestion and thermal denaturation. In addition, the features of these antimicrobial molecules make them suitable for use in animal farming, such as aquaculture. Fmoc solid phase peptide synthesis on 2-chlorotrityl chlorine (CTC) resin using the “tea-bag” approach was conducted to generate the VarvA cyclotide identified previously from Viola arvensis. MALDI-TOF mass spectrometry determined the correct peptide amino acid sequence and the cyclization sites-critical in this multicyclic compound. The cyclotide showed antimicrobial activity against various Gram-negative bacteria, including recurrent pathogens present in Chilean aquaculture. The highest antimicrobial activity was found to be against Flavobacterium psychrophilum. In addition, membrane blebbing on the bacterial surface after exposure to the cyclotide was visualized by SEM microscopy and the Sytox Green permeabilization assay showed the ability to disrupt the bacterial membrane. We postulate that this compound can be proposed for the control of fish farming infections.

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“…Cysteinreste wurden mit S ‐Acetamidomethyl(Acm)‐Schutzgruppe eingeführt, und die Peptid‐Faltung erfolgte durch Cyclisierung zum 1,2,3‐Triazol über CuAAC (CuSO 4 /Ascorbinsäure generieren in situ den Cu I ‐Katalysator);14 dem schloss sich die Disulfidbrückenbildung durch Iod in Methanol/Wasser an 16. Dies lieferte Hybridpeptide ( 2 – 9 ) in guter Ausbeute (SI: Tabelle 2S).…”

Section: Methodsunclassified

Stabilisierung eines cysteinreichen Kegelschneckentoxins, MrIA, in Form eines 1,2,3‐Triazol‐Disulfidbrückenmimetikums

et al. 2014

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Die Synthese von Disulfidbrückenmimetika ist eine wichtige Strategie zur Optimierung disulfidreicher Peptide beim Wirkstoff-Design. Wir beschreiben Mimetika des Conotoxins MrIA, die durch selektiven Austausch einzelner Disulfidbindungen gegen Brücken aus einem 1,4-disubstituierten 1,2,3-Triazol erhalten wurden. Eine sequenzielle, Kupfer-katalysierte Azid-Alkin-Klick-Reaktion (CuAAC) mit nachfolgender Disulfidbildung führte regioselektiv zu hybriden Triazol-Disulfid-Analoga von MrIA. Mimetika, in denen Triazol die Cys4-Cys13-Disulfidbindung ersetzte, behielten ihre Tertiärstruktur sowie die volle In-vitro-und In-vivo-Aktivität als Inhibitoren der Noradrenalin-Wiederaufnahme bei. Diese Mimetika sind resistent gegen Reduktion mit Glutathion, was zu einer verbesserten Plasmastabilität führt und dadurch interessant für die Wirkstoff-Entwicklung ist.Schema 1. A) Disulfid-Faltung führt zu mehreren Isomeren, disulfidreiche Peptide sind anfällig für "S-S-Austausch". B) Disulfid-/1,2,3-Triazol-Faltung liefert nur eines der mçglichen Isomere.

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Comparative evaluation of different methods for disulfide bond formation in synthesis of the HIV‐2 antigenic determinant

Cited by 31 publications

References 5 publications

Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation

Large Scale Solid Phase Synthesis of Peptide Drugs: Use of Commercial Anion Exchange Resin as Quenching Agent for Removal of Iodine during Disulphide Bond Formation

Chemical Synthesis and Functional Analysis of VarvA Cyclotide

Stabilisierung eines cysteinreichen Kegelschneckentoxins, MrIA, in Form eines 1,2,3‐Triazol‐Disulfidbrückenmimetikums

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