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.
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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
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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
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DOI: https://doi.org/10.1007/978-1-0716-2489-0_3
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