Synthesis and Application of Fmoc‐His(3‐Bum)‐OH

Abstract

This paper presents a reevaluation of the synthesis and properties of Fmoc-His(3-Bum)-OH regarding its application in SPPS with minimal racemization of histidine residues during coupling and esterification reactions. By-product formation during the deprotection of the test peptides could be significantly reduced by scavenging the concomitantly formed HCHO, e.g. with methoxyamine.

Amino Acid-Protecting Groups

“…404 -N π -tert-Butoxymethyl (Bum). 405,406 It is removed by TFA and resistant to hydrogenolysis. Formylation during its removal can be prevented using appropiate scavengers in the same way as for Bom.…”

Aqueous microwave-assisted solid-phase peptide synthesis using Fmoc strategy. III: Racemization studies and water-based synthesis of histidine-containing peptides

“…The literature lists several methods for the quantification of racemization of amino acids in general and of His in particular. Mergler and coworkers used the simple tripeptide, Phe-L-His-Gly-NH 2 , as a suitable model to study the racemization of L-His during SPPS using the Fmoc strategy (Robertson et al 1999;Mergler et al 2001). Therefore, we used this tripeptide as a model in a racemization study of water-based SPPS using amino acid nanoparticles.…”

“…This side reaction is one of the biggest concerns in the course of the total synthesis of biologically active peptides and their analogs. His has a basic imidazole ring that is well known to readily lead to serious racemization via the withdrawing a-proton of His (Mergler et al 2001). Although many N improtecting groups for imidazole ring of His have been reported, none completely suppress racemization.…”

Disulfide Formation Strategies in Peptide Synthesis

“…[39] However, carbodiimides are not equally efficient with respect to phosphonium and uronium reagents, and switching to another coupling system for Cys introduction is not practical, especially when using automated peptide synthesizers. [60] The model peptide H-Gly-Cys-Phe-NH 2 was prepared by the uronium activation method and used to determine the levels of racemization with the protecting groups MBom, Trt, and Acm. [60] The model peptide H-Gly-Cys-Phe-NH 2 was prepared by the uronium activation method and used to determine the levels of racemization with the protecting groups MBom, Trt, and Acm.…”