Application of dehydroalanine as a building block for the synthesis of selenocysteine-containing peptides

Abstract

Selenocysteine (Sec), the 21 st proteinogenic amino acid, is inserted co-translationally into number of natural proteins. It is coded by a dual function stop codon UGA (opal). It is a redox active amino acid found at the active sites of several enzymes that are involved in oxidation-reduction reactions. These enzymes include the three major mammalian selenoproteins glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and iodothyronine deiodinase (Dio). Although Sec is structurally similar to its sulfur analogue cysteine (Cys), the lower pK a of the selenol group in Sec as compared to that of Cys and the interesting redox properties of the selenium atom in peptides and proteins play crucial roles in redox catalysis. However, the chemical synthesis of Sec-containing peptides has been a difficult task. In this paper, we report on a new method for the synthesis of Sec and Sec-containing peptides using dehydroalanine (Dha) as a building block.

Selenium‐NMR Spectroscopy in Organic Synthesis: From Structural Characterization Toward New Investigations

“…Another example of synthesis of selenocysteine-containing peptides was reported in 2019 by Reddy and Mugesh. [114] They demonstrated a new route employing the dehydroalanine (Dha), a widely used precursor for protein modification, to incorporate the Sec amino acid into the peptide. Once Dha was prepared, it was carried out the synthesis of Sec derivatives and Sec dipeptides (Scheme 19).…”

Asymmetric Synthesis with Organoselenium Compounds – The Past Twelve Years

“…Alemán and Marini [79] and their coworkers performed the asymmetric additions of enolates of α‐seleno ketones like 98 to vinyl nitro compounds in the presence of chiral catalysts such as 92 and its congeners, while an enantioselective addition of the enolate of 2‐indolone 99 to N ‐phenylmaleimide, using the binaphthyl catalysts 100 a and 100 b was reported by Shirakawa et al [59] . In a substrate‐controlled process, Reddy and Mugesh [80] prepared a series of redox‐active peptides such as 102 as mixtures of diastereomers by the conjugate addition of benzylic selenolates to dehydroamino acid residues (e. g. 101 ). The selenolates were generated from the reduction of the corresponding diselenides or selenocyanates with sodium borohydride.…”

A high-throughput platform for efficient exploration of functional polypeptide chemical space

“…Reactive functional groups such as alkenes and alkynes were also facilely grafted to the side chain (P5 and P6). 77 Photolabile o-nitro benzyl group was efficiently incorporated (P8) for potential light-responsive materials 78 . We also generated various anionic and cationic polyelectrolytes bearing diverse functionalities such as carboxylic acids, primary, secondary, tertiary amines, and quaternary ammonium (P9-P19).…”