64 research outputs found
Synthesis of (+)-Cortistatin A
Steroids have historically elicited attention from the chemical sciences owing to their utility in living systems, as well as their intrinsic and diverse beauty.1 The cortistatin family (Figure 1, 1-7 and others),2 a collection of unusual, marine 9-(10,19)-abeo-androstane steroids, is certainly no exception; aside from challenging stereochemistry and an odd bricolage of functional groups, the salient feature of these sponge metabolites is, inescapably, their biological activity. Cortistatin A, the most potent member of the small family, inhibits the proliferation of human umbilical vein endothelial cells (HUVECs, IC50) 1.8 nM), evidently with no general toxicity toward either healthy or cancerous cell lines (IC50(testing cells)/IC50(HUVECs) g 3300).2a From initial pharmacological studies, binding appears to occur reversibly, but to an unknown target, inhibiting the phosphorylation of an unidentified 110 kDa protein, and implying a pathway that may be unique to know
The Initial and Final States of Electron and Energy Transfer Processes: Diabatization as Motivated by System-Solvent Interactions
For a system which undergoes electron or energy transfer in a polar solvent, we define the diabatic states to be the initial and final states of the system, before and after the nonequilibrium transfer process. We consider two models for the system-solvent interactions: A solvent which is linearly polarized in space and a solvent which responds linearly to the system. From these models, we derive two new schemes for obtaining diabatic states from ab initio calculations of the isolated system in the absence of solvent. These algorithms resemble standard approaches for orbital localization, namely, the Boys and EdmistonāRuedenberg (ER) formalisms. We show that Boys localization is appropriate for describing electron transfer [ Subotnik et al., J. Chem. Phys. 129, 244101 (2008) ] while ER describes both electron and energy transfer. Neither the Boys nor the ER methods require definitions of donor or acceptor fragments and both are computationally inexpensive. We investigate one chemical example, the case of oligomethylphenyl-3, and we provide attachment/detachment plots whereby the ER diabatic states are seen to have localized electron-hole pairs
Quantum walk on distinguishable non-interacting many-particles and indistinguishable two-particle
We present an investigation of many-particle quantum walks in systems of
non-interacting distinguishable particles. Along with a redistribution of the
many-particle density profile we show that the collective evolution of the
many-particle system resembles the single-particle quantum walk evolution when
the number of steps is greater than the number of particles in the system. For
non-uniform initial states we show that the quantum walks can be effectively
used to separate the basis states of the particle in position space and
grouping like state together. We also discuss a two-particle quantum walk on a
two- dimensional lattice and demonstrate an evolution leading to the
localization of both particles at the center of the lattice. Finally we discuss
the outcome of a quantum walk of two indistinguishable particles interacting at
some point during the evolution.Comment: 8 pages, 7 figures, To appear in special issue: "quantum walks" to be
published in Quantum Information Processin
Long-Range Effects on Calcium Binding and Conformational Change in the N-Domain of Calmodulinā
Proteins within the EF-hand protein family exhibit different conformational responses to Ca2+ binding. Calmodulin and other members of the EF-hand protein family undergo major changes in conformation upon binding Ca2+. However, some EF-hand proteins, such as calbindin D9k (Clb), bind Ca2+ without a significant change in conformation. Here, we investigate the effects of replacement of a leucine at position 39 of the N-terminal domain of calmodulin (N-Cam) with a phenylalanine derived from Clb. This variant is studied alone and in the context of other mutations that affect the conformational properties of N-Cam. Strikingly, the introduction of Phe39, which is distant from the calcium binding sites, leads to a significant enhancement of Ca2+ binding affinity, even in the context of other mutations which trap the protein in the closed form. The results yield novel insights into the evolution of EF-hand proteins as calcium sensors versus calcium buffers
Stereocontrolled Synthesis of Kalihinol C
We report a concise chemical synthesis
of kalihinol C via a possible
biosynthetic intermediate, āprotokalihinolā, which was
targeted as a scaffold en route to antiplasmodial analogs. High stereocontrol
of the kalihinol framework relies on a heterodendralene cascade to
establish the target stereotetrad. Common problems of regio- and chemoselectivity
encountered in the kalihinol class are explained and solved
Synthesis of Lepadiformine Using a Hydroamination Transform
Dissection of lepadiformine
by a double hydroamination transform
affords a simple achiral amino diene. This reaction is accomplished
in the forward sense by amine-directed hydroboration and an oxidative
alkyl shift to nitrogen, both of which occur with high stereoselectivity
to generate three stereogenic centers and the lepadiformine skeleton
Stereocontrolled Synthesis of Kalihinol C
We report a concise chemical synthesis
of kalihinol C via a possible
biosynthetic intermediate, āprotokalihinolā, which was
targeted as a scaffold en route to antiplasmodial analogs. High stereocontrol
of the kalihinol framework relies on a heterodendralene cascade to
establish the target stereotetrad. Common problems of regio- and chemoselectivity
encountered in the kalihinol class are explained and solved
Synthesis of (ā)-Neothiobinupharidine
An eight step, asymmetric synthesis of a dimeric thiaspirane
nuphar
alkaloid from 3-methyl-2-cyclo-pentenone is reported. The brevity
of the route relies on a useful procedure for tandem reductive allylation
of cyclopentenones, as well as the minimization of redox manipulations
and other functional group interconversions. The distribution of products
that arise from spontaneous dimerization points to a more complex
biosynthesis
Synthesis of (ā)-Neothiobinupharidine
An eight step, asymmetric synthesis of a dimeric thiaspirane
nuphar
alkaloid from 3-methyl-2-cyclo-pentenone is reported. The brevity
of the route relies on a useful procedure for tandem reductive allylation
of cyclopentenones, as well as the minimization of redox manipulations
and other functional group interconversions. The distribution of products
that arise from spontaneous dimerization points to a more complex
biosynthesis
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