NEOGLYCOPROTEIN SYNTHESIS USING THE COPPER-CATALYZED AZIDE–ALKYNE CLICK REACTION AND NATIVE CHEMICAL LIGATION - Click Chemistry in Glycoscience: New Developments and Strategies - page 252

H 2 N-His-Gly-Val-Thr-Ser-Ala-Pro-Glu-Thr-Arg-Pro-Ala-Pro-Gly-Ser-Thr-Ala-Pro-Pro-Ala-OH

(a)

H 2 N-His-Gly-Val- Pra -Ser-Ala-Pro-Glu-Thr-Arg-Pro-Ala-Pro-Gly-Ser-Thr-Ala-Pro-Pro-Ala-OH

9

H 2 N-His-Gly-Val- Pra - Pra -Ala-Pro-Glu-Thr-Arg-Pro-Ala-Pro-Gly-Ser-Thr-Ala-Pro-Pro-Ala-OH

10

H 2 N-His-Gly-Val- Pra -Ser-Ala-Pro-Glu-Thr-Arg-Pro-Ala-Pro-Gly-Ser- Pra -Ala-Pro-Pro-Ala-OH

11

H 2 N-His-Gly-Val- Pra -Ser-Ala-Pro-Glu- Pra -Arg-Pro-Ala-Pro-Gly-Ser- Pra -Ala-Pro-Pro-Ala-OH

12

H 2 N-His-Gly-Val- Pra - Pra -Ala-Pro-Glu-Thr-Arg-Pro-Ala-Pro-Gly- Pra - Pra -Ala-Pro-Pro-Ala-OH

13

H 2 N-His-Gly-Val- Pra - Pra -Ala-Pro-Glu- Pra -Arg-Pro-Ala-Pro-Gly- Pra - Pra -Ala-Pro-Pro-Ala-OH

14

(b)

FIGURE 10.1 (a) The MUC1 repeat sequence, with the five possible glycosylation sites
highlighted. (b) The propargylated peptides 9 - 14 synthesized [34].

subsequently subjected to CuAAC reactions with alkynyl sugars using standard con-
ditions, but unfortunately large amounts of copper catalyst and sodium ascorbate
reducing agent were required to enable the reaction to proceed. Under these reaction
conditions, significant amounts of side products were observed and that complicated
the subsequent purification.
The use of large quantities of copper catalyst seems to be a common phenomenon,
with equimolar or even excess copper used during the on-resin global click gly-
coconjugation of alkynyl-substituted peptoids [35], the synthesis of triazole-linked
peptide-oligonucleotide conjugates [36], and the ligation of a peptide-azide and a
peptide-alkyne to form dimers [37]. This is in stark contrast to the usual catalytic
0.2 eq. [24], 0.1 eq. [25, 26c], and even down to 0.05 [30a] copper equivalents used