ISSN:
1573-3904
Keywords:
Difficult sequence
;
Diketopiperazine
;
Solid-phase peptide synthesis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary This paper describes the synthesis of the bradykinin B1 antagonist [desArg10]HOE 140 (d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Tic-Oic-OH) by the solid-phase method. This synthesis is predicted to be a difficult one because the C-terminal sequence d-Tic-Oic, when linked to the resin, could easily undergo an intramolecular aminolysis, releasing the corresponding diketopiperazine. This reaction is greatly favored by the imino acidic structure of these two residues and by the d-configuration of the second one. When using the Fmoc strategy, the reaction takes place during the Fmoc removal with piperidine. In this case, it has been suggested previously that it is possible to prevent the side reaction by reducing the time of the base treatment. In our hands, this expedient worked correctly for the synthesis of a test tetrapeptide (H-Gly-Pro3-OH), but under the same conditions the synthesis of the target peptide failed completely. In contrast, the use of the very hindered 2-chlorotrityl resin reduced diketopiperazine formation to undetectable levels.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00119994
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