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Related Concept Videos

SN1 Reaction: Stereochemistry02:15

SN1 Reaction: Stereochemistry

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This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
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SN1 Reaction: Kinetics02:05

SN1 Reaction: Kinetics

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In an SN2 reaction, the reaction rate depends on both the type of nucleophile and the substrate. A hindered tertiary alkyl halide is practically inert to the SN2 mechanism despite using a strong nucleophile.
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
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SN1 Reaction: Mechanism02:25

SN1 Reaction: Mechanism

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Kinetic studies of ionization of a tertiary halide in a protic solvent suggest that only the substrate participates in the rate-determining step (slow step). The nucleophile is involved only after the slowest step. The SN1 reaction takes place in a multiple-step mechanism. 
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
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Acidity of 1-Alkynes02:42

Acidity of 1-Alkynes

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The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
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Predator-Prey Interactions02:39

Predator-Prey Interactions

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Predators consume prey for energy. Predators that acquire prey and prey that avoid predation both increase their chances of survival and reproduction (i.e., fitness). Routine predator-prey interactions elicit mutual adaptations that improve predator offenses, such as claws, teeth, and speed, as well as prey defenses, including crypsis, aposematism, and mimicry. Thus, predator-prey interactions resemble an evolutionary arms race.
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Predicting Products: SN1 vs. SN202:27

Predicting Products: SN1 vs. SN2

17.4K
Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
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An In vitro Co-infection Model to Study Plasmodium falciparum-HIV-1 Interactions in Human Primary Monocyte-derived Immune Cells
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Modelling interaction between HIV-1 Nef and calnexin.

Alexei A Adzhubei1,2, Anastasia A Anashkina1, Yaroslav V Tkachev1

  • 1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

AIDS (London, England)
|July 14, 2018
PubMed
Summary

Researchers modeled the interaction between HIV Nef and calnexin, identifying compounds that inhibit this interaction. An analog of a tested compound effectively reversed Nef

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Area of Science:

  • Molecular biology and virology
  • Drug discovery and medicinal chemistry
  • Cardiovascular research

Background:

  • HIV-associated atherosclerosis is a significant comorbidity linked to the virus's impact on cholesterol metabolism.
  • The HIV protein Nef disrupts the maturation of ATP-Binding Cassette (ABCA) 1, a key cellular cholesterol transporter.
  • Nef interferes with ABCA1 maturation by binding to and impairing the function of calnexin, an endoplasmic reticulum chaperone.

Purpose of the Study:

  • To model the interaction interface between HIV Nef and calnexin.
  • To identify small molecule compounds capable of inhibiting the Nef-calnexin interaction.
  • To explore therapeutic strategies for HIV-associated comorbidities.

Main Methods:

  • Molecular dynamics simulations were used to model the calnexin cytoplasmic domain.
  • Global docking and QASDOM software were employed for receptor-ligand complex analysis.
  • Structure-based virtual screening identified potential inhibitory compounds, with one analog tested in vitro.

Main Results:

  • Key interaction sites between calnexin and Nef were identified.
  • Virtual screening revealed small molecules that could block the calnexin interaction site.
  • A Nef inhibitor analog, AMS-55, effectively reversed Nef's negative impact on ABCA1 levels.

Conclusions:

  • The study successfully modeled the Nef-calnexin interaction and identified potential inhibitors.
  • Experimental validation confirmed the effectiveness of a novel inhibitory compound.
  • These findings offer a basis for developing new treatments for HIV-related cardiovascular issues.