Highlights

Electronically tuned N-terminal glycine selective bioconjugation enables in vitro and in vivo species-specific Staphylococcus aureus targeting

The research group of Prof. Vishal Rai [Department of Chemistry] developed “rapi-Gly-tag,” a platform for precision targeting of biomolecules from in vitro to in vivo. The study establishes a versatile approach for the selective modification of N-terminal glycine in small molecules, peptides, and proteins, and demonstrates its potential for selectively detecting and targeting Staphylococcus aureus, an important bacterial pathogen. The team developed electronically tuned reagents to achieve rapid and selective modification of N-terminal glycine through stable covalent bond formation. The technology expands the scope of glycine-selective bioconjugation from small molecules to peptides and proteins. Further, the technology exploits a unique molecular signature in the bacterial cell wall to selectively target S. aureus without targeting other tested bacteria. Unlike earlier approaches, this method maintains its efficiency in complex biological environments. The team demonstrated selective detection in experimental models, including fruit fly larvae and mice. Furthermore, it showed antibacterial activity against drug-susceptible and drug-resistant strains, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), while also inhibiting biofilm formation. These findings establish a promising chemical approach for the selective detection and targeting of bacterial pathogens and open new avenues for developing diagnostic and therapeutic strategies against difficult-to-treat infections.For more details, kindly visit: https://www.nature.com/articles/s41467-026-77959-2