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application in processes relevant to N-S acyl transfer and
peptide transamidation reactions where MPAA has already
been employed advantageously, despite its low solubility under
these conditions.17,28
The Authors acknowledge financial support from EPSRC
(EP/J007560/1) and Dextra Laboratories UK. We are also grate-
ful to Dextra Laboratories UK for providing tetrasaccharide
oxazoline 23.
References
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Scheme 5 Thiol capping and endoglycosidase A mediated elaboration
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from Fig. 2a that a more significant quantity of the initial MESNa
thioester (20) is still present in the 3-MBSA catalysed process
after 1.5 h indicating that the thiol–thioester exchange is slower
for 3-MBSA than for MPAA (Fig. 2b). It is likely that the 3-MBSA
catalysed reaction can be accelerated further by employing the
higher concentrations (0.2 M) that are optimal for MPAA catalysis, 15 J. Kang, N. L. Reynolds, C. Tyrrell, J. R. Dorin and D. Macmillan, Org.
and are more comparable with employing the pre-formed thioester.3
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16 J.-S. Zheng, S. Tang, Y.-C. Huang and L. Liu, Acc. Chem. Res., 2013,
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enhanced polarity enabled straightforward purification of the 17 F. Burlina, G. Papageorgiou, C. Morris, P. D. White and J. Offer,
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18 For clarity results are shown at pH 6. See ESI† for NCL catalysis at
ligation product whereas MPAA co-eluted with it.
After isolation of 19 the Gln-Cys mutation at the Gly–Cys
pH 7 and pH 8.
ligation site was simply carboxamidomethylated to restore a pseudo- 19 M. M. Toteva and J. P. Richard, in Advances in Physical Organic Chemistry,
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20 T. Ueda, K. Tomita, Y. Notsu, T. Ito, M. Fumoto, T. Takakura,
glutamine (‘‘Q’’) residue at this position (Scheme 5). The N-acetyl
glucosamine unit was finally extended to the native N-glycoprotein
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oxazoline (22) in the presence of endoglycosidase A.22,23
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21 See ESI† for the analytical HPLC traces for the 4-MBSA and MPAA
catalysed reactions.
Overall, the results demonstrate that compounds based on the
mercaptobenzyl sulfonate scaffold can accelerate NCL reactions at a 22 W. Huang, Q. Yang, M. Umekawa, K. Yamamoto and L.-X. Wang,
ChemBioChem, 2010, 11, 1350–1355.
23 T. B. Parsons, J. W. B. Moir and A. J. Fairbanks, Org. Biomol. Chem.,
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catalyst and, owing to the increased polarity conferred by the
2009, 7, 3128–3140.
sulfonate group, facilitated straightforward ligation of two GLP-1 24 H. van de Langemheen, A. J. Brouwer, J. Kemmink, J. A. W. Kruijtzer
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25 N. Ollivier, J. Dheur, R. Mhidia, A. Blanpain and O. Melnyk, Org.
fragments, and isolation of the product. MPAA can be significantly
removed from ligation reaction upon acidification and repeated
Lett., 2010, 12, 5238–5241.
extraction of the reaction mixture,24,25 or by using MPAA hydrazide 26 T. Moyal, H. P. Hemantha, P. Siman, M. Refua and A. Brik, Chem.
Sci., 2013, 4, 2496–2501.
27 It has also been shown that MPAA can be replaced with non-aryl
analogues which can be captured on suitably functionalised solid
supports.26,27 However it is hoped that the additional flexibility
thiol 2,2,2-trifluoroethane thiol, which catalyses NCL reactions at a rate
´
provided by 3-MBSA may allow purification of peptide products
without these additional handling steps. Furthermore the high
solubility of these aryl thiols, and further analogues such as
mercaptobenzyl phosphonates, at low pH may additionally find
comparable with MPAA: R. E. Thompson, X. Liu, N. Alonso-Garcıa,
P. J. B. Pereira, K. A. Jolliffe and R. J. Payne, J. Am. Chem. Soc., 2014, 136,
8161–8164.
28 N. Ollivier, A. Blanpain, E. Boll, L. Raibaut, H. Drobecq and
O. Melnyk, Org. Lett., 2014, 16, 4032–4035.
3210 | Chem. Commun., 2015, 51, 3208--3210
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