Biomedical Engineering Reference
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O
O
O
H
N
H
N
OH
C
12
H
25
O
O
O
O
O
O
C
12
H
25
O
NH
1, 2-di-O-lauryl-
rac
-glycero-
3-O-N
a
-acetyl-L-Arginine
Hydrochloride
NH
+
H
2
N
C
12
H
25
OH
NH
2
+
+
H
2
N
Cl
-
NH
2
+
C
12
H
25
Cl
-
1. 65°C, C.
antarctica
lipase
(-H
2
O)
2. Chromatographic purification
N
a
-acetyl-L-Arginine
Methyl Ester Hydrochloride
+
O
O
O
O
H
N
OH
H
N
O
HO
OH
O
OH
O
O
OH
O
rac
-1-O-(N
a
-acetyl-L-Argininyl)
Glycerol Hydrochloride
(and a small amount of
rac
-2-O
isomer)
1. 50°C, Papain or
candida antarctica
lipase
(-H
2
O)
2. Chromatographic purification
O
NH
C
12
H
25
NH
1, 3-di-O-lauryl-
rac
-glycero-
2-O-N
a
-acetyl-L-Arginine
Hydrochloride
+
H
2
N
NH
2
+
+
H
2
N
Cl
-
NH
2
+
Cl
-
Figure 10.6
Lipase-catalyzed synthesis of di-O-alkyl, O-(N
∝
-acetyl-L-argininyl) glycerol (adapted from Infante
et al
., 2009a).
position of phospholipids, respectively (Xu
et al
., 2008 ; Guo
et al
., 2005 ). In addition, many
lipases catalyze the hydrolysis of acyl groups from the 1-acyl position (Xu
et al
., 2008 ; Guo
et al
., 2005). To convey the current state-of-the-art, a recent paper showed that egg yolk
suspended in aqueous solution that contained Lecitase 10 L, a commercial preparation of
porcine pancreatic phospholipase A
2
developed by Novozymes, Inc., exhibited improved
capability for emulsification in aqueous media (Daimer and Kulozik, 2009).
Lipases and phospholipases are also employed to tailor-make “structured” phospholipids,”
with the goal being to control the surface activity of the bio-based surfactant, and/or
incorporate nutritionally beneficial acyl groups, such as omega-3 fatty acids. A potential
application of structured phospholipids is lung surfactants, used in the treatment of acute
and neonatal distress syndrome (Acosta
et al
., 2009 ). Moreover, phospholipids are the main
component of synthetic lung surfactant products: Exosurf
®
(Glaxo Wellcome, Research
Triangle Park, NC), Surfaxin
®
(Discovery Laboratories, Warrington, PA), Venticute
®
(Altana
Pharma AG, Wesel, Germany), and ALEC
®
(Britannia Pharmaceuticals, Newberry, UK).
Acyl groups esterified to the 1- and 2-glycerol position can be selectively incorporated using
lipases and phospholipases A
1
and A
2
. In addition, phospholipase D
via
hydrolysis and
transphosphatidylation can be used to selectively incorporate specific “head groups”
attached to the phosphate group contained at position 3.
This topic has been thoroughly reviewed (Xu
et al
., 2008 ; Guo
et al
., 2005 ). To provide
an example, medium-chain (caprylic) acyl groups were incorporated into the acetone-
soluble fraction of lecithin, a relatively inexpensive source of phospholipids enriched in
phosphatidylcholine (Hossen and Hernandez, 2005). For one series of reactions, lecithin
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