74 research outputs found
Purification and characterisation of a carboxylesterase from the latex ofSynadenium grantii Hook, ‘f’
Role of water in Protein Aggregation and Amyloid Polymorphism
A variety of neurodegenerative diseases are associated with the formation of
amyloid plaques. Our incomplete understanding of this process underscores the
need to decipher the principles governing protein aggregation. Most
experimental and simulation studies have been interpreted largely from the
perspective of proteins: the role of solvent has been relatively overlooked.
In this Account, we provide a perspective on how interactions with water
affect folding landscapes of A monomers, A oligomer
formation, and protofilament formation in a Sup35 peptide. Simulations show
that the formation of aggregation-prone structures (N) similar to the
structure in the fibril requires overcoming high desolvation barrier. The
mechanism of protofilament formation in a polar Sup35 peptide fragment
illustrates that water dramatically slows down self-assembly. Release of water
trapped in the pores as water wires creates protofilament with a dry interface.
Similarly, one of the main driving force for addition of a solvated monomer to
a preformed fibril is the entropy gain of released water.
We conclude by postulating that two-step model for protein crystallization
must also hold for higher order amyloid structure formation starting from
N. Multiple N structures with varying water content results in a number
of distinct water-laden polymorphic structures. In predominantly hydrophobic
sequences, water accelerates fibril formation. In contrast, water-stabilized
metastable intermediates dramatically slow down fibril growth rates in
hydrophilic sequences.Comment: 27 pages, 4 figures; Accounts of Chemical Research, 201
beta-Lactamase-catalyzed hydrolysis of acyclic depsipeptides and acyl transfer to specific amino acid acceptors.
Chloride (HCl ∕ Cl<sup>−</sup>) dominates inorganic aerosol formation from ammonia in the Indo-Gangetic Plain during winter: modeling and comparison with observations
The Winter Fog Experiment (WiFEX) was an intensive field
campaign conducted at Indira Gandhi International Airport (IGIA) Delhi,
India, in the Indo-Gangetic Plain (IGP) during the winter of 2017–2018.
Here, we report the first comparison in South Asia of high-temporal-resolution simulation of ammonia (NH3) along with ammonium
(NH4+) and total NHx (i.e., NH3+ NH4+) using
the Weather Research and Forecasting model coupled with chemistry (WRF-Chem)
and measurements made using the Monitor for AeRosols and Gases in Ambient
Air (MARGA) at the WiFEX research site. In the present study, we
incorporated the Model for Simulating Aerosol Interactions and Chemistry
(MOSAIC) aerosol scheme into WRF-Chem. Despite simulated total NHx
values and variability often agreeing well with the observations, the model
frequently simulated higher NH3 and lower NH4+ concentrations than the observations. Under the winter conditions of high
relative humidity (RH) in Delhi, hydrogen chloride (HCl) was found to
promote the increase in the particle fraction of NH4+ (which
accounted for 49.5 % of the resolved aerosol in equivalent units), with
chloride (Cl−) (29.7 %) as the primary anion. By contrast, the
absence of chloride (HCl / Cl−) chemistry in the standard WRF-Chem model results in the prediction of sulfate (SO42-) as the
dominant inorganic aerosol anion. To understand the mismatch associated with
the fraction of NHx in the particulate phase (NH4+ / NHx),
we added HCl / Cl− to the model and evaluated the influence of its
chemistry by conducting three sensitivity experiments using the model: no
HCl, base case HCl (using a published waste burning inventory), and
3 × base HCl run. We found that 3 × base HCl increased the
simulated average NH4+ by 13.1 µg m−3 and NHx by
9.8 µg m−3 concentration while reducing the average NH3 by
3.2 µg m−3, which is more in accord with the measurements. Thus
HCl / Cl− chemistry in the model increases total NHx concentration,
which was further demonstrated by reducing NH3 emissions by a factor of
3 (−3 × NH3_EMI) in the 3 × base HCl
simulation. Reducing NH3 emissions in the 3 × base HCl
simulation successfully addressed the discrepancy between measured and
modeled total NHx. We conclude that modeling the fate of NH3 in
Delhi requires a correct chemistry mechanism accounting for chloride
dynamics with accurate inventories of both NH3 and HCl emissions.</p
Orally bioavailable anti-HBV dinucleotide acyloxyalkyl prodrugs
The acyloxyalkyl derivatives of a model anti-HBV dinucleotide were synthesized and evaluated as orally bioavailable prodrugs. Our studies have led to the identification of the first orally bioavailable dinucleotide prodrugs for further therapeutic development against the hepatitis B virus (HBV)
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