Abstract
Over the past 20 years, native chemical ligation has facilitated the synthesis of numerous complex peptide and protein targets, with and without post-translational modifications, as well as the design and construction of a variety of engineered protein variants. This powerful methodology has also served as a platform for the development of related chemoselective ligation technologies which have greatly expanded the scope and flexibility of ligation chemistry. This chapter details a number of important extensions of the original native chemical ligation manifold, with particular focus on the application of new methods in the total chemical synthesis of proteins. Topics covered include the development of auxiliary-based ligation methods, the post-ligation manipulation of Cys residues, and the synthesis and utility of unnatural amino acid building blocks (bearing reactive thiol or selenol functionalities) in chemoselective ligation chemistry. Contemporary applications of these techniques to the total chemical synthesis of peptides and proteins are described.
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Walsh CT, Garneau-Tsodikova S, Gatto GJ Jr (2005) Protein posttranslational modifications: the chemistry of proteome diversifications. Angew Chem Int Ed 44:7342–7372
Walsh C (2006) Posttranslational modification of proteins: expanding nature’s inventory. Roberts and Co Publishers, Englewood, Colo
Dawson PE, Muir TW, Clark-Lewis I, Kent SBH (1994) Synthesis of proteins by native chemical ligation. Science 266:776–779
Wieland T, Bokelmann E, Bauer L, Lang HU, Lau H (1953) Über peptidsynthesen. 8. Mitteilung bildung von S-haltigen peptiden durch intramolekulare wanderung von aminoacylresten. Justus Liebigs Ann Chem 583:129–149
Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2154
Kemp DS, Leung S-L, Kerkman DJ (1981) Models that demonstrate peptide bond formation by prior thiol capture. I. Capture by disulfide formation. Tetrahedron Lett 22:181–184
Kemp DS, Kerkman DJ (1981) Models that demonstrate peptide bond formation by prior thiol capture. II. Capture by organomercury derivatives. Tetrahedron Lett 22:185–186
Fotouhi N, Galakatos NG, Kemp DS (1989) Peptide synthesis by prior thiol capture. 6. Rates of the disulfide-bond-forming capture reaction and demonstration of the overall strategy by synthesis of the C-terminal 29-peptide sequence of BPTI. J Org Chem 54:2803–2817
Liu C-F, Tam JP (1994) Chemical ligation approach to form a peptide bond between unprotected peptide segments. Concept and model study. J Am Chem Soc 116:4149–4153
Liu C-F, Tam JP (1994) Peptide segment ligation strategy without use of protecting groups. Proc Natl Acad Sci U S A 91:6584–6588
Schnoelzer M, Kent SBH (1992) Constructing proteins by dovetailing unprotected synthetic peptides: backbone-engineered HIV protease. Science 256:221–225
Schnoelzer M, Alewood P, Jones A, Alewood D, Kent SBH (1992) In situ neutralization in Boc-chemistry solid phase peptide synthesis. Rapid, high yield assembly of difficult sequences. Int J Pept Protein Res 40:180–193
Hackeng TM, Griffin JH, Dawson PE (1999) Protein synthesis by native chemical ligation: expanded scope by using straightforward methodology. Proc Natl Acad Sci U S A 96:10068–10073
Camarero J, Adeva A, Muir T (2000) 3-Thiopropionic acid as a highly versatile multidetachable thioester resin linker. Lett Pept Sci 7:17–21
Dawson PE, Churchill MJ, Ghadiri MR, Kent SBH (1997) Modulation of reactivity in native chemical ligation through the use of thiol additives. J Am Chem Soc 119:4325–4329
Johnson ECB, Kent SBH (2006) Insights into the mechanism and catalysis of the native chemical ligation reaction. J Am Chem Soc 128:6640–6646
Evans TC Jr, Benner J, Xu MQ (1998) Semisynthesis of cytotoxic proteins using a modified protein splicing element. Protein Sci 7:2256–2264
Muir TW (2003) Semisynthesis of proteins by expressed protein ligation. Annu Rev Biochem 72:249–289
Pollock SB, Kent SB (2011) An investigation into the origin of the dramatically reduced reactivity of peptide-prolyl-thioesters in native chemical ligation. Chem Commun 47:2342–2344
Kent SB (2009) Total chemical synthesis of proteins. Chem Soc Rev 38:338–351
Payne RJ, Wong CH (2010) Advances in chemical ligation strategies for the synthesis of glycopeptides and glycoproteins. Chem Commun 46:21–43
Raibaut L, Ollivier N, Melnyk O (2012) Sequential native peptide ligation strategies for total chemical protein synthesis. Chem Soc Rev 41:7001–7015
Macmillan D (2006) Evolving strategies for protein synthesis converge on native chemical ligation. Angew Chem Int Ed 45:7668–7672
Hackenberger CPR, Schwarzer D (2008) Chemoselective ligation and modification strategies for peptides and proteins. Angew Chem Int Ed 47:10030–10074
Unverzagt C, Kajihara Y (2013) Chemical assembly of N-glycoproteins: a refined toolbox to address a ubiquitous posttranslational modification. Chem Soc Rev 42:4408–4420
Haase C, Seitz O (2008) Extending the scope of native chemical peptide coupling. Angew Chem Int Ed 47:1553–1556
Dirksen A, Dawson PE (2008) Expanding the scope of chemoselective peptide ligations in chemical biology. Curr Opin Chem Biol 12:760–766
Gamblin DP, Scanlan EM, Davis BG (2009) Glycoprotein synthesis: an update. Chem Rev 109:131–163
Okamoto R, Mandal K, Ling M, Luster AD, Kajihara Y, Kent SBH (2014) Total chemical synthesis and biological activities of glycosylated and non-glycosylated forms of the chemokines CCL1 and Ser-CCL1. Angew Chem Int Ed 53:5188–5193
Bang D, Kent SB (2004) A one-pot total synthesis of crambin. Angew Chem Int Ed 43:2534–2538
Blanco-Canosa JB, Dawson PE (2008) An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation. Angew Chem Int Ed 47:6851–6855
Okamoto R, Mandal K, Sawaya MR, Kajihara Y, Yeates TO, Kent SB (2014) (Quasi-)racemic X-ray structures of glycosylated and non-glycosylated forms of the chemokine Ser-CCL1 prepared by total chemical synthesis. Angew Chem Int Ed 53:5194–5198
UniprotKB/TrEMBL Protein Database Release 2014_07 Statistics (2014) http://www.ebi.ac.uk/uniprot/TrEMBLstats. Accessed 1 Sept 2014
Canne LE, Bark SJ, Kent SBH (1996) Extending the applicability of native chemical ligation. J Am Chem Soc 118:5891–5896
Marinzi C, Bark SJ, Offer J, Dawson PE (2001) A new scaffold for amide ligation. Bioorg Med Chem 9:2323–2328
Botti P, Carrasco MR, Kent SBH (2001) Native chemical ligation using removable Nα-(1-phenyl-2-mercaptoethyl) auxiliaries. Tetrahedron Lett 42:1831–1833
Low DW, Hill MG, Carrasco MR, Kent SB, Botti P (2001) Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary. Proc Natl Acad Sci U S A 98:6554–6559
Kawakami T, Aimoto S (2003) A photoremovable ligation auxiliary for use in polypeptide synthesis. Tetrahedron Lett 44:6059–6061
Marinzi C, Offer J, Longhi R, Dawson PE (2004) An o-nitrobenzyl scaffold for peptide ligation: synthesis and applications. Bioorg Med Chem 12:2749–2757
Clive DL, Hisaindee S, Coltart DM (2003) Derivatized amino acids relevant to native peptide synthesis by chemical ligation and acyl transfer. J Org Chem 68:9247–9254
Muir TW, Sondhi D, Cole PA (1998) Expressed protein ligation: a general method for protein engineering. Proc Natl Acad Sci U S A 95:6705–6710
Chatterjee C, McGinty RK, Pellois JP, Muir TW (2007) Auxiliary-mediated site-specific peptide ubiquitylation. Angew Chem Int Ed 46:2814–2818
McGinty RK, Kim J, Chatterjee C, Roeder RG, Muir TW (2008) Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature 453:812–816
Offer J, Dawson PE (2000) N-alpha-2-Mercaptobenzylamine-assisted chemical ligation. Org Lett 2:23–26
Kawakami T, Akaji K, Aimoto S (2001) Peptide bond formation mediated by 4,5-dimethoxy-2-mercaptobenzylamine after periodate oxidation of the N-terminal serine residue. Org Lett 3:1403–1405
Vizzavona J, Dick F, Vorherr T (2002) Synthesis and application of an auxiliary group for chemical ligation at the X-gly site. Bioorg Med Chem Lett 12:1963–1965
Offer J, Boddy CNC, Dawson PE (2002) Extending synthetic access to proteins with a removable acyl transfer auxiliary. J Am Chem Soc 124:4642–4646
Macmillan D, Anderson DW (2004) Rapid synthesis of acyl transfer auxiliaries for cysteine-free native glycopeptide ligation. Org Lett 6:4659–4662
Wu B, Chen J, Warren JD, Chen G, Hua Z, Danishefsky SJ (2006) Building complex glycopeptides: development of a cysteine-free native chemical ligation protocol. Angew Chem Int Ed 45:4116–4125
Chen J, Chen G, Wu B, Wan Q, Tan Z, Hua Z, Danishefsky SJ (2006) Mature homogeneous erythropoietin-level building blocks by chemical synthesis: the EPO 114–166 glycopeptide domain, presenting the O-linked glycophorin. Tetrahedron Lett 47:8013–8016
Kumar KS, Brik A (2010) Accessing posttranslationally modified proteins through thiol positioning. J Pept Sci 16:524–529
Brik A, Yang YY, Ficht S, Wong CH (2006) Sugar-assisted glycopeptide ligation. J Am Chem Soc 128:5626–5627
Brik A, Wong CH (2007) Sugar-assisted ligation for the synthesis of glycopeptides. Chemistry 13:5670–5675
Yan LZ, Dawson PE (2001) Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization. J Am Chem Soc 123:526–533
Brik A, Ficht S, Yang YY, Bennett CS, Wong CH (2006) Sugar-assisted ligation of N-linked glycopeptides with broad sequence tolerance at the ligation junction. J Am Chem Soc 128:15026–15033
Yang YY, Ficht S, Brik A, Wong CH (2007) Sugar-assisted glycoprotein synthesis. J Am Chem Soc 129:7690–7701
Bennett CS, Dean SM, Payne RJ, Ficht S, Brik A, Wong CH (2008) Sugar-assisted glycopeptide ligation with complex oligosaccharides: scope and limitations. J Am Chem Soc 130:11945–11952
Pentelute BL, Kent SBH (2007) Selective desulfurization of cysteine in the presence of Cys(Acm) in polypeptides obtained by native chemical ligation. Org Lett 9:687–690
Ficht S, Payne RJ, Brik A, Wong CH (2007) Second-generation sugar-assisted ligation: a method for the synthesis of cysteine-containing glycopeptides. Angew Chem Int Ed 46:5975–5979
Lutsky MY, Nepomniaschiy N, Brik A (2008) Peptide ligation via side-chain auxiliary. Chem Commun 10:1229–1231
Ajish Kumar KS, Harpaz Z, Haj-Yahya M, Brik A (2009) Side-chain assisted ligation in protein synthesis. Bioorg Med Chem Lett 19:3870–3874
Payne RJ, Ficht S, Tang S, Brik A, Yang YY, Case DA, Wong CH (2007) Extended sugar-assisted glycopeptide ligations: development, scope and applications. J Am Chem Soc 129(44):13527–13536
Payne RJ, Ficht S, Greenberg WA, Wong CH (2008) Cysteine-free peptide and glycopeptide ligation by direct aminolysis. Angew Chem Int Ed 47:4411–4415
Thomas GL, Hsieh YSY, Chun CKY, Cai ZL, Reimers JR, Payne RJ (2011) Peptide ligations accelerated by N-terminal aspartate and glutamate residues. Org Lett 13:4770–4773
Hojo H, Ozawa C, Katayama H, Ueki A, Nakahara Y, Nakahara Y (2010) The mercaptomethyl group facilitates an efficient one-pot ligation at Xaa-Ser/Thr for (glyco)peptide synthesis. Angew Chem Int Ed 49:5318–5321
Chalker JM, Bernardes GJL, Lin YA, Davis BG (2009) Chemical modification of proteins at cysteine: opportunities in chemistry and biology. Chem Asian J 4:630–640
Okamoto R, Kajihara Y (2008) Uncovering a latent ligation site for glycopeptide synthesis. Angew Chem Int Ed 47:5402–5406
Heinrikson RL (1970) Selective S-methylation of cysteine in proteins and peptides. Biochem Biophys Res Commun 41:967–972
Gross E, Morell JL (1974) The reaction of cyanogen bromide with S-methylcysteine: fragmentation of the peptide 14–29 of bovine pancreatic ribonuclease A. Biochem Biophys Res Commun 59:1145–1150
Tam JP, Yu Q (1998) Methionine ligation strategy in the biomimetic synthesis of parathyroid hormones. Biopolymers 46:319–327
Haase C, Rohde H, Seitz O (2008) Native chemical ligation at valine. Angew Chem Int Ed 47:6807–6810
Wan Q, Danishefsky SJ (2007) Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides. Angew Chem Int Ed 46:9248–9252
Hoffmann FW, Ess RJ, Simmons TC, Hanzel RS (1956) The desulfurization of mercaptans with trialkyl phosphites. J Am Chem Soc 78:6414
Walling C, Basedow OH, Savas ES (1960) Some extensions of the reaction of trivalent phosphorus derivatives with alkoxy and thiyl radicals; a new synthesis of thioesters. J Am Chem Soc 82:2181–2184
Walling C, Rabinowitz R (1957) The reaction of thiyl radicals with trialkyl phosphites. J Am Chem Soc 79:5326
Rohde H, Seitz O (2010) Ligation-desulfurization: a powerful combination in the synthesis of peptides and glycopeptides. Biopolymers 94:551–559
Dawson PE (2011) Native chemical ligation combined with desulfurization and deselenization: a general strategy for chemical protein synthesis. Isr J Chem 51:862–867
Chalker JM (2013) Prospects in the total synthesis of protein therapeutics. Chem Biol Drug Des 81:122–135
Johnson EC, Malito E, Shen Y, Rich D, Tang WJ, Kent SB (2007) Modular total chemical synthesis of a human immunodeficiency virus type 1 protease. J Am Chem Soc 129:11480–11490
Zheng J-S, Tang S, Qi Y-K, Wang Z-P, Liu L (2013) Chemical synthesis of proteins using peptide hydrazides as thioester surrogates. Nat Protocols 8:2483–2495
Fang GM, Li YM, Shen F, Huang YC, Li JB, Lin Y, Cui HK, Liu L (2011) Protein chemical synthesis by ligation of peptide hydrazides. Angew Chem Int Ed 50:7645–7649
Fang GM, Wang JX, Liu L (2012) Convergent chemical synthesis of proteins by ligation of peptide hydrazides. Angew Chem Int Ed 51:10347–10350
Wilkinson BL, Stone RS, Capicciotti CJ, Thaysen-Andersen M, Matthews JM, Packer NH, Ben RN, Payne RJ (2012) Total synthesis of homogeneous antifreeze glycopeptides and glycoproteins. Angew Chem Int Ed 51:3606–3610
Garner J, Harding MM (2010) Design and synthesis of antifreeze glycoproteins and mimics. ChemBioChem 11:2489–2498
Peltier R, Brimble MA, Wojnar JM, Williams DE, Evans CW, DeVries AL (2010) Synthesis and antifreeze activity of fish antifreeze glycoproteins and their analogs. Chem Sci 1:538–551
Sakamoto I, Tezuka K, Fukae K, Ishii K, Taduru K, Maeda M, Ouchi M, Yoshida K, Nambu Y, Igarashi J, Hayashi N, Tsuji T, Kajihara Y (2012) Chemical synthesis of homogeneous human glycosyl-interferon-beta that exhibits potent antitumor activity in vivo. J Am Chem Soc 134:5428–5431
Wang P, Dong S, Brailsford JA, Iyer K, Townsend SD, Zhang Q, Hendrickson RC, Shieh J, Moore MAS, Danishefsky SJ (2012) At last: erythropoietin as a single glycoform. Angew Chem Int Ed 51:11576–11584
Wang P, Dong S, Shieh J-H, Peguero E, Hendrickson R, Moore MAS, Danishefsky SJ (2013) Erythropoietin derived by chemical synthesis. Science 342:1357–1360
Murakami M, Okamoto R, Izumi M, Kajihara Y (2012) Chemical synthesis of an erythropoietin glycoform containing a complex-type disialyloligosaccharide. Angew Chem Int Ed 51:3567–3572
Liu S, Pentelute BL, Kent SBH (2012) Convergent chemical synthesis of [lysine24, 38, 83] human erythropoietin. Angew Chem Int Ed 51:993–999
Payne RJ (2013) Total synthesis of erythropoietin through the development and exploitation of enabling synthetic technologies. Angew Chem Int Ed 52:505–507
Warren JD, Miller JS, Keding SJ, Danishefsky SJ (2004) Toward fully synthetic glycoproteins by ultimately convergent routes: a solution to a long-standing problem. J Am Chem Soc 126:6576–6578
Chen G, Warren JD, Chen J, Wu B, Wan Q, Danishefsky SJ (2006) Studies related to the relative thermodynamic stability of C-terminal peptidyl esters of O-hydroxy thiophenol: emergence of a doable strategy for non-cysteine ligation applicable to the chemical synthesis of glycopeptides. J Am Chem Soc 128:7460–7462
Wong CTT, Tung CL, Li X (2013) Synthetic cysteine surrogates used in native chemical ligation. Mol Biosyst 9:826–833
Botti P, Tchertchian S (2006) Side chain extended ligation. WO/2006/133962
Crich D, Banerjee A (2007) Native chemical ligation at phenylalanine. J Am Chem Soc 129:10064–10065
Easton CJ, Hutton CA, Tan EW, Tiekink ERT (1990) Synthesis of homochiral hydroxy-α-amino acid derivatives. Tetrahedron Lett 31:7059–7062
Easton CJ, Hutton CA, Roselt PD, Tiekink ERT (1994) Stereocontrolled synthesis of β-hydroxyphenylalanine and β-hydroxytyrosine derivatives. Tetrahedron 50:7327–7340
Crich D, Banerjee A (2006) Expedient synthesis of threo-beta-hydroxy-alpha-amino acid derivatives: phenylalanine, tyrosine, histidine, and tryptophan. J Org Chem 71:7106–7109
Chen J, Wan Q, Yuan Y, Zhu JL, Danishefsky SJ (2008) Native chemical ligation at valine: a contribution to peptide and glycopeptide synthesis. Angew Chem Int Ed 47:8521–8524
Chen J, Wang P, Zhu JL, Wan Q, Danishefsky SJ (2010) A program for ligation at threonine sites: application to the controlled total synthesis of glycopeptides. Tetrahedron 66:2277–2283
Yang RL, Pasunooti KK, Li FP, Liu XW, Liu CF (2009) Dual native chemical ligation at lysine. J Am Chem Soc 131:13592–13593
Marin J, Didierjean C, Aubry A, Casimir JR, Briand JP, Guichard G (2004) Synthesis of enantiopure 4-hydroxypipecolate and 4-hydroxylysine derivatives from a common 4,6-dioxopiperidinecarboxylate precursor. J Org Chem 69:130–141
Ajish Kumar KS, Haj-Yahya M, Olschewski D, Lashuel HA, Brik A (2009) Highly efficient and chemoselective peptide ubiquitylation. Angew Chem Int Ed 48:8090–8094
El Oualid F, Merkx R, Ekkebus R, Hameed DS, Smit JJ, de Jong A, Hilkmann H, Sixma TK, Ovaa H (2010) Chemical synthesis of ubiquitin, ubiquitin-based probes, and diubiquitin. Angew Chem Int Ed 49:10149–10153
Hejjaoui M, Haj-Yahya M, Kumar KS, Brik A, Lashuel HA (2011) Towards elucidation of the role of ubiquitination in the pathogenesis of Parkinson’s disease with semisynthetic ubiquitinated alpha-synuclein. Angew Chem Int Ed 50:405–409
Merkx R, de Bruin G, Kruithof A, van den Bergh T, Snip E, Lutz M, El Oualid F, Ovaa H (2013) Scalable synthesis of γ-thiolysine starting from lysine and a side by side comparison with δ-thiolysine in non-enzymatic ubiquitination. Chem Sci 4:4494–4498
Kumar KS, Bavikar SN, Spasser L, Moyal T, Ohayon S, Brik A (2011) Total chemical synthesis of a 304 amino acid K48-linked tetraubiquitin protein. Angew Chem Int Ed 50:6137–6141
Tan ZP, Shang SY, Danishefsky SJ (2010) Insights into the finer issues of native chemical ligation: an approach to cascade ligations. Angew Chem Int Ed 49:9500–9503
Harpaz Z, Siman P, Kumar KSA, Brik A (2010) Protein synthesis assisted by native chemical ligation at leucine. ChemBioChem 11:1232–1235
Shang SY, Tan ZP, Dong SW, Danishefsky SJ (2011) An advance in proline ligation. J Am Chem Soc 133:10784–10786
Dong S, Shang S, Tan Z, Danishefsky SJ (2011) Toward homogeneous erythropoietin: application of metal free dethiylation in the chemical synthesis of the Ala79-Arg166 glycopeptide domain. Isr J Chem 51:968–976
Townsend SD, Tan Z, Dong S, Shang S, Brailsford JA, Danishefsky SJ (2012) Advances in proline ligation. J Am Chem Soc 134:3912–3916
Ding H, Shigenaga A, Sato K, Morishita K, Otaka A (2011) Dual kinetically controlled native chemical ligation using a combination of sulfanylproline and sulfanylethylanilide peptide. Org Lett 13:5588–5591
Raibaut L, El Mahdi O, Melnyk O (2014) Solid phase protein chemical synthesis. Topics Curr Chem. doi:10.1007/128_2014_609
Siman P, Karthikeyan SV, Brik A (2012) Native chemical ligation at glutamine. Org Lett 14:1520–1523
Garner P (1984) Stereocontrolled addition to a penaldic acid equivalent: an asymmetric synthesis of threo-β-hydroxy-L-glutamic acid. Tetrahedron Lett 25:5855–5858
Malins LR, Cergol KM, Payne RJ (2013) Peptide ligation-desulfurization chemistry at arginine. ChemBioChem 14:559–563
Bang D, Pentelute BL, Kent SB (2006) Kinetically controlled ligation for the convergent chemical synthesis of proteins. Angew Chem Int Ed 45:3985–3988
Durek T, Torbeev VY, Kent SB (2007) Convergent chemical synthesis and high-resolution X-ray structure of human lysozyme. Proc Natl Acad Sci U S A 104:4846–4851
Torbeev VY, Kent SB (2007) Convergent chemical synthesis and crystal structure of a 203 amino acid “covalent dimer” HIV-1 protease enzyme molecule. Angew Chem Int Ed 46:1667–1670
Thompson RE, Chan B, Radom L, Jolliffe KA, Payne RJ (2013) Chemoselective peptide ligation-desulfurization at aspartate. Angew Chem Int Ed 52:9723–9727
Guan X, Drake MR, Tan Z (2013) Total synthesis of human galanin-like peptide through an aspartic acid ligation. Org Lett 15:6128–6131
Thompson RE, Liu X, Alonso-García N, Pereira PJB, Jolliffe KA, Payne RJ (2014) Trifluoroethanethiol: an additive for efficient one-pot peptide ligation − desulfurization chemistry. J Am Chem Soc 136:8161–8164
Rohde H, Schmalisch J, Harpaz Z, Diezmann F, Seitz O (2011) Ascorbate as an alternative to thiol additives in native chemical ligation. ChemBioChem 12:1396–1400
Moyal T, Hemantha HP, Siman P, Refua M, Brik A (2013) Highly efficient one-pot ligation and desulfurization. Chem Sci 4:2496–2501
Siman P, Blatt O, Moyal T, Danieli T, Lebendiker M, Lashuel HA, Friedler A, Brik A (2011) Chemical synthesis and expression of the HIV-1 Rev protein. ChemBioChem 12:1097–1104
Cergol KM, Thompson RE, Malins LR, Turner P, Payne RJ (2014) One-pot peptide ligation-desulfurization at glutamate. Org Lett 16:290–293
Malins LR, Cergol KM, Payne RJ (2014) Chemoselective sulfenylation and peptide ligation at tryptophan. Chem Sci 5:260–266
Scoffone E, Fontana A, Rocchi R (1966) Selective modification of tryptophan residue in peptides and proteins using sulfenyl halides. Biochem Biophys Res Commun 25:170–174
Scoffone E, Fontana A, Rocchi R (1968) Sulfenyl halides as modifying reagents for polypeptides and proteins. I. Modification of tryptophan residues. Biochemistry 7:971–979
Wilchek M, Miron T (1972) Conversion of tryptophan to 2-thioltryptophan in peptides and proteins. Biochem Biophys Res Commun 47:1015–1020
Shang S, Tan Z, Danishefsky SJ (2011) Application of the logic of cysteine-free native chemical ligation to the synthesis of human parathyroid hormone (hPTH). Proc Natl Acad Sci U S A 108:5986–5989
Bock A, Forchhammer K, Heider J, Leinfelder W, Sawers G, Veprek B, Zinoni F (1991) Selenocysteine: the 21st amino acid. Mol Microbiol 5:515–520
Lobanov AV, Hatfield DL, Gladyshev VN (2009) Eukaryotic selenoproteins and selenoproteomes. Biochim Biophys Acta 1790:1424–1428
Gieselman MD, Xie L, van Der Donk WA (2001) Synthesis of a selenocysteine-containing peptide by native chemical ligation. Org Lett 3:1331–1334
Quaderer R, Sewing A, Hilvert D (2001) Selenocysteine-mediated native chemical ligation. Helv Chim Acta 84:1197–1206
Hondal RJ, Nilsson BL, Raines RT (2001) Selenocysteine in native chemical ligation and expressed protein ligation. J Am Chem Soc 123:5140–5141
Huber R, Criddle RS (1967) Comparison of the chemical properties of selenocysteine and selenocystine with their sulfur analogs. Arch Biochem Biophys 122:164–173
Arnold AP, Tan KS, Rabenstein DL (1986) Nuclear magnetic resonance studies of the solution chemistry of metal complexes. 23. Complexation of methylmercury by selenohydryl-containing amino acids and related molecules. Inorg Chem 25:2433–2437
Pleasants JC, Guo W, Rabenstein DL (1989) A comparative study of the kinetics of selenol/diselenide and thiol/disulfide exchange reactions. J Am Chem Soc 111:6553–6558
Besse D, Siedler F, Diercks T, Kessler H, Moroder L (1997) The redox potential of selenocystine in unconstrained cyclic peptides. Angew Chem Int Ed 36:883–885
Nauser T, Dockheer S, Kissner R, Koppenol WH (2006) Catalysis of electron transfer by selenocysteine. Biochemistry 45:6038–6043
Metanis N, Keinan E, Dawson PE (2010) Traceless ligation of cysteine peptides using selective deselenization. Angew Chem Int Ed 49:7049–7053
Berry SM, Gieselman MD, Nilges MJ, Van der Donk WA, Lu Y (2002) An engineered azurin variant containing a selenocysteine copper ligand. J Am Chem Soc 124:2084–2085
Quaderer R, Hilvert D (2002) Selenocysteine-mediated backbone cyclization of unprotected peptides followed by alkylation, oxidative elimination or reduction of the selenol. Chem Commun 2620–2621
Malins LR, Mitchell NJ, Payne RJ (2014) Peptide ligation chemistry at selenol amino acids. J Pept Sci 20:64–77
Chalker JM, Bernardes GJL, Davis BG (2011) A “tag-and-modify” approach to site-selective protein modification. Acc Chem Res 44:730–741
Malins LR, Payne RJ (2012) Synthesis and utility of beta-selenol-phenylalanine for native chemical ligation-deselenization chemistry. Org Lett 14:3142–3145
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Malins, L.R., Payne, R.J. (2014). Modern Extensions of Native Chemical Ligation for Chemical Protein Synthesis. In: Liu, L. (eds) Protein Ligation and Total Synthesis I. Topics in Current Chemistry, vol 362. Springer, Cham. https://doi.org/10.1007/128_2014_584
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