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Updated: Mar 29, 2026

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
Published on: March 6, 2013
Total chemical synthesis of pentameric cholera toxin subunit B
Paul Spaltenstein1, Samuel R Scherer1, Tyler E Jones1
1Department of Biochemistry, University of Utah, 15 North Medical Drive East, Room 4100, Salt Lake City, UT, 84112, USA. kay@biochem.utah.edu.
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.
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Cholera
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