2025/01/07 by Christy J. Cho, Sangyoon Kang, Conrado Pedebos +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Materials Science · #Advanced biosensing and bioanalysis techniques #Click Chemistry and Applications #Supramolecular Self-Assembly in Materials
paper · doi:10.1002/anie.202421932
openalex publication_date 2025/01/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Abstract Membrane‐forming phospholipids are generated in cells by enzymatic diacylation of non‐amphiphilic polar head groups. Analogous non‐enzymatic processes may have been relevant at the origin of life and could have practical utility in membrane synthesis. However, aqueous head group diacylation is challenging in the absence of enzymes. The use of charged peptides instead of canonical phospholipid head groups offers advantages with respect to ease of acylation and chemical diversity. Here we demonstrate that native chemical ligation (NCL) enables in situ synthesis of diacylated lipopeptides (D‐ALPs), which spontaneously self‐assemble into micron‐sized vesicles resembling cellular membranes. Diacylation occurs between non‐amphiphilic peptides possessing an N ‐terminal cysteine, and acyl thioesters. Peptide head groups endow unique membrane functions, which is demonstrated by incorporation of an arginine‐glycine‐aspartic acid (RGD) motif, resulting in vesicle targeting to α v β 3 integrin‐overexpressing cancer cells. The biocompatibility and functional group programmability of D‐ALPs supports their broad utility as membrane mimetics.