Biomedical Engineering Reference
In-Depth Information
ring oxygen has been replaced by nitrogen have gained much interest as
inhibitors of glucosidases. Many of these, natural as well as synthetic, can
be considered SAAs.
Thus, SAAs representing a-, b-, g- and d-amino acids have been pre-
pared, while others are better viewed as dipeptide isosteres or mimetics
(for a review of SAA structures, see [39]; see also [34]). SAAs most often
contain 3-, 4-, 5- and 6-membered rings; in this chapter we will focus on
5- and 6-membered rings, i.e. furanosides and pyranosides. SAAs are thus
conformationally restricted and are used as constrained amino acids, turn
mimetics, or as mimetics of cyclic peptides (Figure 5.7). Containing
amino and carboxylic acid functional groups, SAAs are particularly
well suited as peptidomimetic scaffolds.
OH
HOOC
HOOC
HOOC
O
O
O
O
HO
HO
HO
HO
HO
HO
HO
HO
COOH
NH
2
NH
2
HO
NH
2
NH
2
HO
OCH
3
β
-SAA
γ
-SAA
δ
-SAA (also
β
-anomer)
δ
-SAA, Gum (also epimer)
O
OH
OH
HO
OH
HO
HO
OH
HO
OH
HO
O
HO
O
O
O
HN
O
O
HN
COOH
HN
OCH
3
NH
γ
-turn mimetic
β
-turn mimetic
flexible
-turn mimetic
dipeptide isostere
β
linear dipeptide isostere
Figure 5.7 Examples of some SAAs and their structural use. Above are SAAs in
4
C
1
conformation, below are their respective structural roles. For example, the b-SAA can
mimic a g-turn when incorporated into a peptide, whereas the g-SAA can mimic a
b-turn [34]. Gum is a C-glycosyl glucuronic acid
Kessler, Overhand and coworkers have reported a detailed conforma-
tional study of cyclic tetra- and pentamers containing one or two furanoid
e-sugar amino acids [40]. For example, a tetramer containing three
a-amino acids and a furanoid e-SAA corresponds to a pentapeptide of
a-amino acids, except that it has one additional carbon atom due to the
SAA (Figure 5.8). As the SAA contains a furan ring, the conformational
analysis relies on concepts from nucleoside conformations. In a tetramer
containing two a-amino acids and two copies of this SAA, the two SAAs
adopted different conformations, one of which has a b-turn-like
9-member internal hydrogen-bond ring structure. This is in contrast to
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