# Total chemical synthesis of pentameric cholera toxin subunit B

## TL;DR

Scientists chemically synthesized a key cholera toxin component and its mirror-image version, which could help develop new treatments for cholera.

## Contribution

The first total chemical synthesis of l-CtxB and d-CtxB using a three-segment ligation approach for potential d-peptide drug discovery.

## Key findings

- Oxidative folding successfully produced functional 62 kDa pentameric l-CtxB capable of GM1 ligand binding.
- Mirror-image d-CtxB is now available for use in mirror-image phage display to discover toxin-neutralizing d-peptides.

## Abstract

Vibrio cholerae annually infects millions worldwide, causing intense and life-threatening diarrheal disease. The pentameric cholera toxin subunit B (CtxB) binds to the ganglioside GM1 on epithelial cells, initiating endocytosis and downstream toxicity. We present the total chemical protein synthesis of l-CtxB and mirror-image d-CtxB using a three-segment N-to-C native chemical ligation approach. Oxidative folding produced the desired 62 kDa pentameric proteins, with l-CtxB capable of binding native GM1 ligand. Synthetic d-CtxB is now ready to serve as a target in mirror-image phage display, representing a significant milestone for the discovery of toxin-neutralizing d-peptides to treat and prevent cholera.

Vibrio cholerae annually infects millions worldwide, causing intense and life-threatening diarrheal disease.