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© 2008 SCIENCE
J. AM. CHEM. SOC.
the magnesium content
by mass spectrometry.
In the presence of a carboxyl-rich peptide
similar to ones associated with calcification
in relevant marine organisms, calcite
grew 25 to 50% faster and had up to 3 mol
% higher magnesium content, which helps
account for the discrepancies. A difference
this large corresponds to an offset in temperature
of 7 to 14 ºC.—CD
REDEFINING A PROTEIN
Despite its short length, a molecule consisting
of 10 amino acids designed by a
Japan-based team more closely resembles
a protein than a peptide in structural and
theoretical studies. In
light of examining the
tiny protein, the researchers
propose
that specific
biophysical
properties
based upon
how a molecule
folds should be
the measure
of whether
that molecule
is considered a
Ensemble of
NMR structural
conformations of
the 10-amino acid
protein CLN025.
AFM images reveal
different “steps”
growing from a
dislocation in calcite
in the absence (top)
and presence (bottom)
of magnesium and
carboxyl-rich peptides.
protein, without
any rigid cutoffs with
respect to size (J.
Am. Chem. Soc., DOI:
10.1021/ja8030533).
By rule, the cutoff between
peptides and proteins is currently 50
amino acids. Shinya Honda and colleagues
at the National Institute of Advanced
Industrial Science & Technology (AIST),
in Tsukuba, synthesized the 10-residue
molecule, called CLN025. X-ray crystal
structure information was consistent with
NMR studies in solution, showing that
CLN025 has a well-defined 3-D structure.
In addition, molecular dynamics simulations
of CLN025’s folding process indicate
that the structure the AIST team observed
is considerably more stable than other possible
conformations. CLN025 may prove
valuable for studying microscopic events
in protein folding, says theoretical chemist
Peter G. Wolynes of the University of California,
San Diego.—CD
PROBING HEAT IN
MOLECULAR JUNCTIONS
Israeli researchers have directly measured
the effective temperature of current-carrying
molecular junctions in an electronic
device by using surface-enhanced Raman
spectroscopy (SERS) (Nat. Nanotechnol.,
DOI: 10.1038/nnano.2008.304). Molecular
junctions, which are circuit structures that
consist of a few or even just one molecule
straddling a pair of electrodes, offer extreme
miniaturization advantages for electronic
device designers. But these junctions are
fragile and sensitive to temperature, which
varies with current flow. Only indirect
methods for gauging junction temperatures
have been reported so
far. For example, some methods
are based on measuring the rate at
which chains of metal atoms rupture.
Tel Aviv University chemists
Ori Cheshnovsky, Yoram Selzer,
and coworkers have now prepared
temperature-probe devices in which
4,4'-biphenyldithiol molecules form
junctions with silver electrodes.
The team used a SERS microscope
to measure Raman scattering while
current flowed through those junctions.
Then from the intensity of the measured
Raman signals, which are associated with
molecular vibrations, the group determined
the junction temperature as a function of
applied voltage.—MJ
NEW LEADS FOUND FOR
ALZHEIMER’S THERAPIES
Two research groups have independently
published findings related to Alzheimer’s
disease treatments. Both experimental
therapies target amyloid β, the protein believed
to cause the disease. Weihong Song
of the University of British Columbia, Vancouver,
and colleagues treated mice with
valproic acid, a compound already used as
an anticonvulsant and mood stabilizer for
patients with epilepsy, bipolar disorder, and
other conditions. They found that valproic
acid reduced enzymatic production of amyloid
β by γ-secretase. The treatment prevented
brain cell death and axon damage
and improved memory in mice that were
in early stages of Alzheimer’s (J. Exp. Med.,
DOI: 10.1084/jem.20081588). Li Gan of the
University of California, San Francisco, and
coworkers took another approach. Instead
of limiting the formation of amyloid β, they
opted to increase its degradation in mice.
The researchers boosted the activity of
cathepsin B—an enzyme that breaks down
amyloid β—by reducing levels of cystatin
C, an enzyme that inhibits cathepsin B activity.
The mice in the experiment showed
improvements in learning and memory
(Neuron 2008, 60, 247).—SLR
HYDROGEL-FORMING
PRODRUG AIDS DELIVERY
A water-loving drug modified with a hydrophobic
fatty acid tail has been found to selfassemble
into a hydrogel that can enmesh a
Enzyme
catalysis
BREAKING UP Acetaminophen (blue)
with a fatty acid tail forms a hydrogel that
can carry a second agent, curcumin (red);
an enzyme can release the drugs.
second agent. The hydrogel can then be dissolved
enzymatically, enabling it to serve as
a two-agent delivery vehicle (Biomaterials,
DOI: 10.1016/j.biomaterials.2008.09.045).
“To the best of our knowledge, there are
no previous reports on developing single
and multiple drug-delivery vehicles from
self-assembled prodrugs,” note Jeffrey M.
Karp of Brigham & Women’s Hospital, in
Boston; George John of the City College of
New York; and coworkers, who carried out
the study. The researchers derivatized acetaminophen
with a fatty acid. This turns the
drug into an amphiphilic prodrug that selfassembles
into a hydrogel. The researchers
showed that the hydrogel can encapsulate a
second agent, the anti-inflammatory agent
curcumin. Exposure to lipase degrades
the hydrogel, releasing the two agents; the
nontoxic fatty acid is a by-product. “This
approach has an advantage over polymerbased
prodrugs that generate polymer fragments
with heterogeneous chain lengths
upon degradation that may present complex
toxicity profiles,” the researchers write.—SB
WWW.CEN-ONLINE.ORG 23 NOVEMBER 3, 2008