C O M M U N I C A T I O N S
Figure 2. Photographs of vesicular formation at the interface of PUPC and PAPC upon hydration. Arrows show (A) the PUPC/PAPC interface, (B, C)
PUPC and PAPC dispersions are moving toward the recognition interface, (D, E) “wall extension” at a rate of about 5 µm per second (bars ) 30 µm).
Next, we investigated the supramolecular structures formed by these
m
ketal-based nucleolipids. Below their T values and at a concentration
above 4% w/w, both nucleolipids form hydrogels. Above their T
m
values, we observed the formation of large lamellar systems upon
hydration with no major differences observed between PUPC and
PAPC lipids (Figure 1). TEM images show heterogeneous vesicles
for both PUPC and PAPC samples (Figure 1, insets, and SI).
The formation of supramolecular assemblies in the presence of these
two nucleolipids was investigated. Separately lipids PUPC and PAPC
exist in a fluid state at room temperature and, as noted earlier, organize
into lamellar systems upon hydration. However, when the two comple-
mentary lipids are hydrated in close proximity to each other a new
supramolecular structure spontaneously forms at the interface in a few
seconds. For this experiment, solid PUPC and PAPC are loaded on a
glass slide opposite each other and separated by a distance of 0.5 mm.
Real time photographs show that upon hydration the two lamellar systems
approach each other and upon contact form a wall of vesicles at the
interface (Figure 2; See movie in SI). Numerous small vesicles (<50 µm)
are present in this wall of vesicles as well as fusions with larger ones.
The molecular recognition and vesicular formation event occur rapidly
and we can estimate a vesicle wall extension rate of about 5 µm per second.
Similarly in solution, the mixture of PUPC and PAPC gives spontaneously
Figure 3. Molecular models of the proposed amphiphile structures in the
south conformation (C2′ endo conformation of U and A derivatives left
and right, respectively).
specific lipid-based supramolecular assemblies via programmed or
encoded small molecules.
Acknowledgment. L.M. and P.B. acknowledge financial support
from the Army Research Office. M.W.G. acknowledges support
from BU. N.T. acknowledges support from “Association Fran c¸ aise
contre les Myopathies” (AFM).
Supporting Information Available: Synthesis of compounds 3 and
6
, transmission electron micrographs, and molecular modeling details
and movie. This material is available free of charge via the Internet at
http://pubs.acs.org.
m
a macroscopic assembly at a temperature higher than T , whereas control
samples made of PUPC/PUPC or PAPC/ PAPC mixtures do not. TEM
experiments confirm that the PUPC/PAPC assembly is a lamellar system
composed of a mixture of closely associated heterogeneous vesicles with
numerous very small vesicles and/or buds, which are not observed for
pure samples. When the mixing experiment (in solution or on a glass slide)
is repeated with analogues of the nucleolipids lacking the ketal chains or
the complementary base pairing, assembly formation is not evident
demonstrating the important role of the hydrophobic ketal chains and base
pair recognition.
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11
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1
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12,13
such phenomenon.
Continued research is this area will provide
key design requirements and understandings toward synthesizing
JA805974G
J. AM. CHEM. SOC. 9 VOL. 130, NO. 44, 2008 14455