Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Mm-imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N-ethy1-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by IH-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Mm-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the ma1eimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs.

Alkylation of histidine with maleimido-compounds / A.M. PAPINI; S. RUDOLPH; G. SIGLMÜLLER; H.-J. MUSIOL; W. GÖHRING; L. MORODER. - In: INTERNATIONAL JOURNAL OF PEPTIDE & PROTEIN RESEARCH. - ISSN 0367-8377. - STAMPA. - 39:(1992), pp. 348-355.

Alkylation of histidine with maleimido-compounds.

PAPINI, ANNA MARIA;
1992

Abstract

Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Mm-imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N-ethy1-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by IH-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Mm-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the ma1eimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs.
1992
39
348
355
A.M. PAPINI; S. RUDOLPH; G. SIGLMÜLLER; H.-J. MUSIOL; W. GÖHRING; L. MORODER
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/219574
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