β2AR: old horse’s new tricks

It’s almost four years since the Nobel prize in chemistry went to Brian Kobilka and Robert Lefkowitz for their contribution in our understanding of G protein-coupled receptor (GPCR) signaling. They did their most exciting work by studying β2 adrenergic receptor (β2AR). Yet, despite the titanic efforts, the receptor still holds lots of secrets from us.

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OC tidbits #6

Nicolaou et al. (JACS)

Nicolaou et al. does some medicinal chemistry on prostaglandins. Take a look at this Bobbit‘s salt protocol for deprotection/oxidation combo. It seems like they overload the reaction, compared to the original paper, which used 3 equivalents of the oxidant, but who cares if it works?

Moragas et al (ACIE)

Unprecedented (c) sigmatropic rearrangement of aziridines into sulfoximines.

And De Kimpe’s rearrangement for comparison.

Li et al (ACIE)

I’m not sure I would buy the proposed mechanism for the conversion below. The authors skip ‘−H₂‘ step and get away with it by simply writing “the imine intermediate 44 […] underwent tautomerization and a key decarboxylation to generate 45 with higher oxidation state.” Something else is clearly happening under that −CO₂ arrow and it’s not mere tautomerization.

Wappes et al (ACIE)

So similar, yet so different halogens. I guess, NaF won’t give anything useful under these conditions.

 

No fail no gain

While astronomers recently have been celebrating great discoveries (gravitational waves from colliding black holes keep rolling), at the opposite end of matter size ruler things don’t look as brightly. For instance, the search for ‘sterile’ neutrinos didn’t spot anything, despite the IceCube, a massive 2-km long neutrino detector buried in the Antarctic ice.

Skepticism about synaptic nanocolumns

Couple of days ago I’ve come across a recent paper in Nature with quite an eyebrow-raising title “A trans-synaptic nanocolumn aligns neurotransmitter release to receptors“. The title made me think as if the authors have observed hitherto unknown structures in the synaptic cleft. That would be quite a sensation! But then this sentence comes in the abstract:

These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins^{4, 5, 6}, suggesting the existence of a trans-synaptic molecular ‘nanocolumn’.

Now it looked like they propose some kind of neuroscience equivalent of dark matter. You know, something that nobody knows what it is, but that certainly must be there, otherwise there’s no explanation to what we see.