Selenolysine: A New Tool for Traceless Isopeptide Bond Formation

Abstract

Despite their biological importance,p ost-translationally modified proteins are notoriously difficult to produce in ahomogeneous fashionb yusing conventionalexpressions ystems. Chemical protein synthesis or semisynthesis offers as olutiont ot his problem;h owever,t raditional strategies often rely on sulfur-based chemistry that is incompatiblew ith the presence of any cysteine residues in the target protein. To overcome these limitations,w e presentt he design and synthesis of g-selenolysine, as elenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of g-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to ap eptide segment of human glucokinase.T he resultingp olypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotectedc ysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptidesm arks it as au niversal handlef or conjugating any ubiquitin-like modifying protein to its target.

A Shelf Stable Fmoc Hydrazine Resin for the Synthesis of Peptide Hydrazides

“…17 This method avoids the need for strong oxidizing conditions, enabling broader compatibility with common synthetic peptide functionalities, and has been widely adopted in a broad range of applications. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The increased use of C-terminal α-hydrazides in peptide chemistry creates a demand for robust synthetic tools for accessing these moieties. A number of methods have been published to allow access to C-terminal hydrazides on both synthetic 15,16,38 and expressed 15,39,40 peptides and proteins.…”

Toward Enantiomerically Pure β-Seleno-α-amino Acids via Stereoselective Se-Michael Additions to Chiral Dehydroalanines

“…Recently, selenium-containing analogues of modified Lys residues have been developed in order to facilitate traceless isopeptide bond formation through isopeptide chemical ligation. 15 In addition, it is well-known that 4-selenalysine (SeLys) has been used as a substitute for Lys to synthesize artificial lanthipeptides from in vitro translation. 16 In general, the introduction of selenium in the skeleton of amino acid involves the use of disodium diselenide and tert-butyl (2chloroethyl)carbamate to obtain the respective selenium-based nucleophile di-tert-butyl (diselanediylbis(ethane-2,1-diyl))dicarbamate, which is able to react in situ through an S N 2 reaction with N-Boc-β-bromoalanine methyl ester giving the corresponding protected SeLys.…”