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OH
OH
OH
OH
O
O
VAZO44
SH
+
S
(eq. a)
O
(HO)
3
(HO)
3
O
and/or h
ν
NH
2
NH
2
aqueous solvent
Hag
OH
O
OH
HO
HO
SH
O
OH
HO
HO
S
44
(eq. b)
protein
protein
OH
VAZO44 and/or h
ν
Ss
G-Hag43
SCHEME 3.18
Davis glycosylation of Hag (eq. a) and Hag-containing protein (eq. b)
It is worth mentioning at this point that while our work described above was in
progress, Davis and coworkers reported the synthesis of
S
-glycosyl amino acids via
photoinduced addition of glycosyl thiols to homoallylglycine (Hag) (Scheme 3.18,
equation a) [38]. This work was propaedeutic to the development of a convergent
approach to
S
-glycosylated proteins via TEC. In fact, Hag was site-specifically intro-
duced into a number of proteins by gene sequence design and the resulting alkenyl
proteins were allowed to react with glycosyl thiols to give the target
S
-glycosylated
proteins in almost quantitative yields (Scheme 3.18, equation b). Notably, as a demon-
stration of the power of TEC, the glycoconjugation reaction to a virus-like nanopar-
ticle, obtained by self-assembly of the Q
-(Hag16) protein, occurred with complete
consumption of all 180 ene functional groups, thus establishing a record for a multiple
hydrothiolation of the same substrate via TEC.
Given this knowledge, we were motivated to develop our own TEC and TYC-
based strategies for post-synthetic glycosylation of peptides and proteins. To this aim
we set out to follow two approaches both starting from cysteine-containing peptides
and proteins (Scheme 3.19). One approach entailed the introduction of a chemical
handle bearing an alkene tag followed by TEC between this group and a sugar thiol
OH
O
OH
L
HO
O
S
SH
X
X
peptide or
protein
HO
S
route A
S
X
peptide or
protein
S
-glycoside
SH
peptide or
protein
OH
OH
O
O
HO
S
HO
peptide or
protein
route B
C
-glycoside
SCHEME 3.19
Routes toward post-synthetic peptide and protein glycosylation via TEC.
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