Peptide Synthesis
Formamidine Linker for the Reversible Crosslinking of Two Alkyl Amines in Peptide Stapling
Precise Construction of an Antimicrobial Peptide Targeting Bacterial Cell Membranes Derived From Natural Peptides.
Overcoming Proteolytic Instability in a β-Turn Antimicrobial Peptide via Cyclization and Stereochemical Inversion to Combat MDR Bacteria
Fluorescent Macrocyclization: Metal-Free Coupling Based on Glycine and Salicylaldehyde Enables One-Step Peptide Labeling and Cyclization
Water-Based Amino Acid Coupling Technology for Sustainable Solid-Phase Peptide Synthesis
How Are Peptides Synthesized? A Comprehensive Guide to Modern Methodologies
Light-Driven Boron-Carbon Bond Construction: Synthesis of Carboranyl Peptides Targeting BNCT
Lightweight AI Tool AMPLiT Unearths Potent Antimicrobial Peptides from Millennia-Old Coprolites
Today, we share important research, soon to be published in Nature Communications, titled "Identification of antimicrobial peptides from ancient gut microbiomes." This study, by developing a lightweight artificial intelligence tool named AMPLiT, systematically analyzed metagenomic data from seven ancient human fecal fossils (coprolites) dating back 1000-2000 years. It successfully uncovered 160 potential antimicrobial peptide (AMP) candidates. Experimental validation showed that among the 40 peptides successfully synthesized, 36 (90%) exhibited significant antibacterial activity in vitro. Remarkably, approximately two-thirds of the active antimicrobial peptides originated from Segatella copri(formerly Prevotella copri), a dominant symbiotic bacterium in ancient guts whose prevalence has significantly declined in modern populations. These AMPs from ancient microbiomes not only possess membrane-disrupting mechanisms, low cytotoxicity, and low hemolysis risk but also demonstrated efficacy comparable to traditional antibiotics (vancomycin, polymyxin B) in a mouse wound infection model. This work reveals the immense potential of ancient gut microbiomes as a treasure trove for novel antimicrobial peptides, offering a new solution to combat the antibiotic resistance crisis.
Controlled Cyclization Meets Ribosomal Synthesis: The Birth of a New-Generation Bicyclic Peptide Platform
Today, we share important research from the team of Professor Hiroaki Suga at the University of Tokyo, published in Angewandte Chemie International Edition, titled "Ribosomal Synthesis of Topologically Defined Thioisoindole-Bridged Bicyclic Peptides." This study developed a novel synthetic strategy for bicyclic peptides based on thioisoindole bridging. By designing a semicarbazone-protected 2-nicotinoylbenzaldehyde amino acid (Ac-Ala(NtBA)Sc-CME) as a translation initiator, it was efficiently incorporated into peptide chains using a flexible in vitrotranslation (FIT) system. Subsequently, a mild acid treatment triggered an intramolecular bicyclization reaction, successfully constructing structurally precise bicyclic peptides. This method is fully compatible with mRNA display technology, providing a powerful platform for building large-scale, topologically defined bicyclic peptide libraries for drug discovery.