71,251 research outputs found
Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies
Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions could be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain. Theoretical studies using DFT and (RO)MP2 methods were carried out to analyze the influence of the substitution pattern on the cyclization barriers
The Effect of N-Terminal Cyclization on the Function of the HIV Entry Inhibitor 5P12-RANTES.
Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein. It is not known how this cyclization affects the potency of the inhibitor or whether cyclization is necessary for the function of the protein, although the N-terminal region of RANTES has been shown to be critical for receptor interactions, with even small changes having a large effect. We have studied the kinetics of cyclization of 5P12-RANTES as well as N-terminal variations of the protein that either produce an identical cyclized terminus (Glu0) or that cannot similarly cyclize (Asn0, Phe0, Ile0, and Leu0). We find that the half life for N-terminal cyclization of Gln is roughly 20 h at pH 7.3 at 37 °C. However, our results show that cyclization is not necessary for the potency of this protein and that several replacement terminal amino acids produce nearly-equally potent HIV inhibitors while remaining CC chemokine receptor 5 (CCR5) antagonists. This work has ramifications for the production of active 5P12-RANTES for use in the clinic, while also opening the possibility of developing other inhibitors by varying the N-terminus of the protein
Insight in the activity and diastereoselectivity of various Lewis acid catalysts for the citronellal cyclization
Confinement and Viscoelastic effects on Chain Closure Dynamics
Chemical reactions inside cells are typically subject to the effects both of
the cell's confining surfaces and of the viscoelastic behavior of its contents.
In this paper, we show how the outcome of one particular reaction of relevance
to cellular biochemistry - the diffusion-limited cyclization of long chain
polymers - is influenced by such confinement and crowding effects. More
specifically, starting from the Rouse model of polymer dynamics, and invoking
the Wilemski-Fixman approximation, we determine the scaling relationship
between the mean closure time t_{c} of a flexible chain (no excluded volume or
hydrodynamic interactions) and the length N of its contour under the following
separate conditions: (a) confinement of the chain to a sphere of radius D, and
(b) modulation of its dynamics by colored Gaussian noise. Among other results,
we find that in case (a) when D is much smaller than the size of the chain,
t_{c}\simND^{2}, and that in case (b), t_{c}\simN^{2/(2-2H)}, H being a number
between 1/2 and 1 that characterizes the decay of the noise correlations. H is
not known \`a priori, but values of about 0.7 have been used in the successful
characterization of protein conformational dynamics. At this value of H
(selected for purposes of illustration), t_{c}\simN^3.4, the high scaling
exponent reflecting the slow relaxation of the chain in a viscoelastic medium
DNA cyclization and looping in the wormlike limit: normal modes and the validity of the harmonic approximation
For much of the last three decades Monte Carlo-simulation methods have been
the standard approach for accurately calculating the cyclization probability,
, or J factor, for DNA models having sequence-dependent bends or
inhomogeneous bending flexibility. Within the last ten years, however,
approaches based on harmonic analysis of semi-flexible polymer models have been
introduced, which offer much greater computational efficiency than Monte Carlo
techniques. These methods consider the ensemble of molecular conformations in
terms of harmonic fluctuations about a well-defined elastic-energy minimum.
However, the harmonic approximation is only applicable for small systems,
because the accessible conformation space of larger systems is increasingly
dominated by anharmonic contributions. In the case of computed values of the J
factor, deviations of the harmonic approximation from the exact value of as
a function of DNA length have not been characterized. Using a recent,
numerically exact method that accounts for both anharmonic and harmonic
contributions to for wormlike chains of arbitrary size, we report here the
apparent error that results from neglecting anharmonic behavior. For wormlike
chains having contour lengths less than four times the persistence length the
error in arising from the harmonic approximation is generally small,
amounting to free energies less than the thermal energy, . For larger
systems, however, the deviations between harmonic and exact values increase
approximately linearly with size.Comment: 23 pages, 6 figures. Typos corrected. Manuscript improve
Iodoarene-Catalyzed Cyclizations of Unsaturated Amides
The cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions is presented. Five-, six-, and seven-membered rings with a range of substitutions can be prepared by this route. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible
Assembly of cyclic hydrocarbons from ethene and propene in acid zeolite catalysis to produce active catalytic sites for MTO conversion
Effects of Sequence Disorder on DNA Looping and Cyclization
Effects of sequence disorder on looping and cyclization of the
double-stranded DNA are studied theoretically. Both random intrinsic curvature
and inhomogeneous bending rigidity are found to result in a remarkably wide
distribution of cyclization probabilities. For short DNA segments, the range of
the distribution reaches several orders of magnitude for even completely random
sequences. The ensemble averaged values of the cyclization probability are also
calculated, and the connection to the recent experiments is discussed.Comment: 8 pages, 4 figures, LaTeX; accepted to Physical Review E; v2: a
substantially revised version; v3: references added, conclusions expanded,
minor editorial corrections to the text; v4: a substantially revised and
expanded version (total number of pages doubled); v5: new Figure 4, captions
expanded, minor editorial improvements to the tex
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