Light‐Driven Diselenide Metathesis in Peptides

Abstract

Peptides containing selenocysteine moieties are susceptible to non‐catalytic reactions of diselenide bonds metathesis induced by visible light. In contrast to previously reported radical metathesis of disulfide bridges in cysteine derivatives, this newly developed reaction is fast and clean, and proceeds without decomposition of peptides and without formation of side products. The diselenide bond in peptides was reported in literature to be more stable than the disulfide one and also less susceptible to metathesis induced by thiols and reducing reagents. We demonstrated that visible light induces fast metathesis of Se−Se bonds in peptides. This reaction is important for the folding of peptides containing selenocysteine residues and may find application in designing dynamic combinatorial libraries of peptides responsive to external influence.

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

“…55 ± 1.88 nm), which is consistent with previous reports [36,52]. The obvious D h difference observed between NCMs and CCMs may be attributed to the intramicellar covalent Se-Se network formation and concomitant shrinkage in the interface between the hydrophobic and hydrophilic portion of the mPEG-P(LA-DSeDEA)-PCL copolymer resulting in a more compact micellar structure [27,33,34]. Both NCMs and CCMs experienced suitable ζ-potentials for cellular attachment and internalization, −9.68 ± 3.03 and −13.1 ± 1.17, respectively.…”

“…Se–Se bonds can also be cleaved by very mild redox signals such as H 2 O 2 and reduced GSH to form seleninic acid and selenol derivatives, respectively [ 62 ]. The observed redox stimuli-responsive propensity was primarily associated with the weak bond energy of the Se–Se bond at 172 kJ/mol [ 25 , 34 , 63 ]. This endowed diselenide containing polymers to be used in the fabrication of redox stimuli-responsive CCMs for the delivery and controlled release of CAs in tumor tissue.…”

“…Obviously, the relatively lower DLC and EE of CCMs might be ascribed to diselenide exchange prompted crosslinking and subsequent core shrinkage and efflux of DOX. Recently, DCBs have been incorporated in supramolecular chemistry and smart material fabrication [23,34,42]. Interestingly, dynamic Se-Se bonds can undergo exchange or metathesis reactions to form new Se-Se, Se-S and, Se-Te bonds when subjected to light stimuli of different wavelengths [59][60][61].…”

“…Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer (Scheme 1) with pendant selenocystamine (Sec) groups by employing the ring-opening polymerization (ROP), hydrolysis, and EDC/NHS coupling reactions. The amphiphilic copolymer self-assembled into stable CCMs owing to visible light-induced diselenide metathesis reactions between the Sec moieties [23,25,34]. In this copolymer architecture, the biocompatible and FDA approved hydrophilic mPEG segment would form the shell of the micelles and help to avoid the non-specific interactions between serum proteins, cellular structures, and the micelles surface.…”

Visible Light‐Mediated Functionalization of Selenocystine‐Containing Peptides

“…Visible light‐initiated generation of selenyl radicals with subsequent addition to terminal [32,33] or internal [34] alkynes has also been investigated. Significantly, catalyst‐free conditions can be used to realize both visible light‐induced metathesis reactions between diselenides and ditellurides [35] and diselenide metathesis between simple diorganyl diselenides [36] or Se−Se bond‐containing peptides [37] . Strikingly, there has been no profound study on selenocysteine (Sec)‐containing peptide modification under visible light conditions.…”