Abstract
Serine/threonine ligation (STL) and cysteine/penicillamine ligation (CPL) are highly chemo- and regioselective reactions between unprotected peptides with C-terminus salicylaldehyde esters and unprotected peptides with N-terminus serine/threonine or cysteine/penicillamine, which serve as powerful tools for cyclic peptide natural product and chemical protein synthesis. Herein, we introduce the preparation of C-terminal peptide salicylaldehyde esters, serine/threonine ligation, cysteine/penicillamine ligation, and subsequent acidolysis.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Liu H, Li X (2018) Serine/threonine ligation: origin, mechanistic aspects, and applications. Acc Chem Res 51:1643–1655
Tan Y, Li J, Jin K, Liu J, Chen Z, Yang J, Li X (2020) Cysteine/penicillamine ligation independent of terminal steric demands for chemical protein synthesis. Angew Chem Int Ed 59:12741–12745
Lee CL, Liu H, Wong CTT et al (2016) Enabling N-to-C ser/thr ligation for convergent protein synthesis via combining chemical ligation approaches. J Am Chem Soc 138:10477–10484
Xu C, Lam HY, Zhang Y, Li X (2013) Convergent synthesis of MUC1 glycopeptides via serine ligation. Chem Commun 49:6200–6202
Li X, Lam HY, Zhang Y, Chan CK (2010) Salicylaldehyde ester-induced chemoselective peptide ligations: enabling generation of natural peptidic linkages at the serine/threonine sites. Org Lett 12:1724–1727
Zhang Y, Li T, Li X (2013) Synthesis of human growth hormone-releasing hormone via three-fragment serine/threonine ligation (STL). Org Biomol Chem 11:5584–5587
Li T, Liu H, Li X (2016) Chemical synthesis of HMGA1a proteins with post-translational modifications via ser/thr ligation. Org Lett 18:5944–5947
Liu H, Liu H, Li X (2019) Use of serine/threonine ligation for the total chemical synthesis of HMGA1a protein with site-specific lysine acetylations. ChemPlusChem 84:779–785
Lam HY, Zhang Y, Liu H, Xu J, Wong CTT, Xu C, Li X (2013) Total synthesis of daptomycin by cyclization via a chemoselective serine ligation. J Am Chem Soc 135:6272–6279
Jin K, Sam IH, Po KHL, Lin D, Ghazvini Zadeh EH, Chen S, Yuan Y, Li X (2016) Total Synthesis of Teixobactin Nat Commun 7:12394
Jin K, Po KHL, Wang S, Reuven JA, Wai CN, Lau HT, Chan TH, Chen S, Li X (2017) Synthesis and structure-activity relationship of teixobactin analogues via convergent ser ligation. Bioorg Med Chem 25:4990–4995
Jin K, Po KHL, Kong WY, Lo CH, Lo CW, Lam HY, Sirinimal A, Reuven JA, Chen S, Li X (2018) Synthesis and antibacterial studies of Teixobactin analogues with non-isostere substitution of enduracididine. Bioorg Med Chem 26:1062–1068
Wong CTT, Lam HY, Li X (2013) Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of tryptophan residues: synthesis of Cyclomontanin B. Org Biomol Chem 11:7616–7620
Wong CTT, Lam HY, Li X (2014) Effective synthesis of cyclic peptide Yunnanin C and analogues via Ser/Thr ligation (STL)- mediated peptide cyclization. Tetrahedron 70:7770–7773
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Liu, J., Li, X. (2022). Serine/Threonine Ligation and Cysteine/Penicillamine Ligation. In: Li, X. (eds) Chemical Protein Synthesis. Methods in Molecular Biology, vol 2530. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2489-0_3
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2489-0_3
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2488-3
Online ISBN: 978-1-0716-2489-0
eBook Packages: Springer Protocols