Selenazolidine: a selenium containing proline surrogate in peptide science. Issue 34 (10th August 2016)

• Record Type: Journal Article
• Authors: Cordeau, E.; Cantel, S.; Gagne, D.; Lebrun, A.; Martinez, J.; Subra, G.; Enjalbal, C.
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 34(2016)
• Page Start: 8101
• Page End: 8108
• Publication Date: 2016-08-10
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob01450j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : In the search for new peptide ligands containing selenium in their sequences, we investigatedl -4-selenazolidine-carboxylic acid (selenazolidine, Sez) as a proline analog with the chalcogen atom in the γ-position of the ring. Abstract : In the search for new peptide ligands containing selenium in their sequences, we investigatedl -4-selenazolidine-carboxylic acid (selenazolidine, Sez) as a proline analog with the chalcogen atom in the γ-position of the ring. In contrast to proteinogenic selenocysteine (Sec) and selenomethionine (SeMet), the incorporation within a peptide sequence of such a non-natural amino acid has never been studied. There is thus a great interest in increasing the possibility of selenium insertion within peptides, especially for sequences that do not possess a sulfur containing amino acid (Cys or Met), by offering other selenated residues suitable for peptide synthesis protocols. Herein, we have evaluated selenazolidine in Boc/Bzl and Fmoc/ t Bu strategies through the synthesis of a model tripeptide, both in solution and on a solid support. Special attention was paid to the stability of the Sez residue in basic conditions. Thus, generic protocols have been optimized to synthesize Sez-containing peptides, through the use of an Fmoc-Xxx-Sez-OH dipeptide unit. As an example, a new analog of the vasopressin receptor-1A antagonist was prepared, in which Pro was replaced with Sez [3-(4-hydroxyphenyl)-propionyl-d -Tyr(Me)-Phe-Gln-Asn-Arg-Sez-Arg-NH2 ]. Both proline and such pseudo-proline containing peptides exhibited similar pharmacological properties and endopeptidase stabilities indicating that the presence of the selenium atom has minimal functional effects. Taking into account the straightforward handling of Sez as a dipeptide building block in a conventional Fmoc/ t Bu SPPS strategy, this result suggested a wide range of potential uses of the Sez amino acid in peptide chemistry, for instance as a viable proline surrogate as well as a selenium probe, complementary to Sec and SeMet, for NMR and mass spectrometry analytical purposes.