Year: 2026
Type: preprint
Abstract: Although some organic selenocompounds exhibit significant therapeutic potential, synthetic access to selenopeptides remains severely limited due to complex postassembly functionalizations strategies. To overcome these limitations, we developed a stable, ebselen-derived lysine compatible with standard Fmoc/tBu solid-phase peptide synthesis (SPPS). We synthesized the Fmoc-Lys(Ebs)-OH building block in five steps, characterizing it by HRMS and NMR spectroscopy. We then evaluated its chemical stability in standard SPPS conditions by assembling a test tripeptide and a diverse tetrapeptide library containing a variety of aminoacids. The novel Fmoc-Lys(Ebs)-OH demonstrated excellent coupling efficiency and high stability, tolerating repeated basic deprotections, couplings and strong acid cleavage to yield selenopeptides without degradation or byproducts. This novel building block enables the direct, site-specific incorporation of ebselen during SPPS, avoiding labor-intensive post-synthetic modifications to access to complex organoselenium peptides for biological and structure-activity relationship studies.
Source: ChemRxiv
Institution: Universidad de Granada
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funder: Universidad de Granada
Award: G1556901886
OpenAlex ID: W7208759205