Some call chemistry the “central science” and it’s not hard to see why. The huge range of projects in which chemistry researchers are involved cross paths with engineering, physics, earth sciences, medicine, and biology. We at Nature Methods are particularly interested in publishing new applications of chemical compounds, tools, or analytical methods that demonstrate potential to provide valuable novel and practical contributions to biology. We’ve got a few very nice papers in our April issue that illustrate this goal well.

From the Department of Chemistry at MIT, Alice Ting and her colleagues have successfully designed a streptavidin tetramer with only one high affinity biotin binding site. While protein chemists will appreciate the design and engineering process, cell biologists will certainly find the mutant streptavidin useful for applications such as cell surface protein labeling. (Listen to Professor Ting speak about this work on Nature’s special Chemistry Podcast.)

We also have a solid contribution from Peter Schultz at the Skaggs Institute for Chemical Biology at Scripps. The Schultz lab has long been a leader in developing and refining a genetic method for incorporating functional unnatural amino acids into proteins; however, the method was somewhat technically challenging for biologists. Now they report a streamlined procedure for using the system in bacteria.

Sometimes, existing chemical tools or methods can find new life in biological applications. Helen Blau and her colleagues at Stanford University discovered that the small organic molecule “Lugal” available in the Promega Beta-Glo Assay System (to quantify β-galactosidase activity in cell culture), could also be used as a bioluminescent reagent to image β-galactosidase activity in living cells.

I welcome comments on these papers and hope to meet with some of you chemists at the ACS meeting with other interesting biological stories to tell!

Allison Doerr, Assistant Editor, Nature Methods

Nature Review Drug Discovery recently posted a “News and Analysis” article by Joanna Owens called “”https://www.nature.com/nrd/journal/vaop/ncurrent/full/nrd2015.html">Funding for accelerating drug development initiative critical," which is about a new initiative launched by the United States Food and Drug Administration called “”https://www.fda.gov/oc/initiatives/criticalpath/“>The Critical Path Initiative.” According to the Critical Path website:

The Critical Path Initiative is FDA’s effort to stimulate and facilitate a national effort to modernize the scientific process through which a potential human drug, biological product, or medical device is transformed from a discovery or “proof of concept” into a medical product.

To achieve this goal, Joanna says that

the FDA announced a list of 76 ‘opportunities’, or projects, for developing new tools that could significantly improve the way that experimental drugs are tested. The opportunities cover six broad topic areas: development of biomarkers; clinical trial designs; bioinformatics; manufacturing; public health needs; and paediatrics.

So it looks like this initiative will complement the NIH Roadmap, which was launched several years ago to “”https://nihroadmap.nih.gov/overview.asp">identify major opportunities and gaps in biomedical research that no single institute at NIH could tackle alone."

I’m not sure if any of our readers are in the pharmaceutical industry, but I would be curious to hear what you think of these initiatives. Do you think that they’ll have a positive impact on human health (i.e. will these initiatives actually accelerate drug discovery and development?) If you don’t think that these initiatives will actually impact the number of new drugs coming to market, what do you think can (or should) be done? And if you are an academic scientist, what do you think about (another) governmental initiative that is focused on drug discovery and development, rather than pure scientific research?

Joshua

Joshua Finkelstein (Associate Editor, Nature)

The 2005 Nobel prize in chemistry went to Yves Chauvin, Robert Grubbs, and Richard Schrock “”https://nobelprize.org/chemistry/laureates/2005/index.html">for the development of the metathesis method in organic synthesis." Olefin metathesis has been used to make a wide range of compounds, including natural products, polymers, and stabilized alpha helices that can inhibit the growth of human leukemia xenografts in vivo.

So it’s not surprising that this field is still really “hot” – you can’t open a chemistry journal without seeing at least one paper involving metathesis… In the March 22nd issue of the Journal of the American Chemical Society, Hong & Grubbs reported that a ruthenium catalyst that had a poly(ethylene glycol) conjugated saturated 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligand was able to catalyze ring-opening metathesis polymerization, ring-closing metathesis, and cross-metathesis reactions in aqueous media (Highly Active Water-Soluble Olefin Metathesis Catalyst).

There’s also a nice minireview by Donohoe et al. that just appeared on Angewandte Chemie International Edition’s Early View – this minireview focused on papers in which ring-closing metathesis was used to synthesize aromatic compounds, including pyrroles, furans, and quinolines (Ring-Closing Metathesis as a Basis for the Construction of Aromatic Compounds).

Although Professor Donohoe won’t be speaking at the upcoming American Chemical Society meeting in Atlanta, Professor Grubbs will give three talks: “”https://oasys2.confex.com/acs/231nm/techprogram/P922810.HTM">Synthesis and applications of ROMP block polymers," “”https://oasys2.confex.com/acs/231nm/techprogram/P921662.HTM">Olefin metathesis catalysts for the synthesis of large and small molecules," “”https://oasys2.confex.com/acs/231nm/techprogram/P948656.HTM">Organic synthesis using the olefin metathesis reactions." Of course, he won’t be the only scientist talking about metathesis at the meeting – there’s a whole session devoted to metathesis on Sunday afternoon (“”https://oasys2.confex.com/acs/231nm/techprogram/S19047.HTM">Recent Developments in Metathesis-Related Processes").

I’ll be attending the upcoming ACS meeting and will be updating this blog regularly – so if you see any of these talks, please feel free to post a comment and let me know what you thought…

Joshua

Joshua Finkelstein (Associate Editor, Nature)

In 2002, Sinninghe Damste et al. showed that two anaerobic ammonium-oxidizing (anammox) bacteria contained a series of unusual lipids that had up to five linearly fused cyclobutane moieties with cis ring junctions (please also see the News & Views piece by Edward DeLong). These bacteria convert nitrite and ammonia into nitrogen gas in an organelle-like structure called the anammoxosome.

These unusual lipids had staircase-like structures, so the authors named these compounds “ladderanes.” They proposed that the presence of these fatty acids turned the anammoxosome membrane into “a tight barrier against diffusion,” which they postulated was necessary to “maintain concentration gradients during the exceptionally slow anammox metabolism and to protect the remainder of the cell from the toxic anammox intermediates” (for example, hydrazine and hydroxylamine).

The enantioselective synthesis of one of these unusual fatty acids – pentacycloanammoxic acid – was recently reported in the March 15th issue of the Journal of the American Chemical Society (Enantioselective Synthesis of Pentacycloanammoxic Acid by Mascitti & Corey). Several years ago, these same authors reported the racemic synthesis of this compound (Total Synthesis of (+/-)-Pentacycloanammoxic Acid), but this is the first enantioselective synthesis of this ladderane and it may be possible to use this enantiomerically pure compound to determine how these “ladderanes” are made in vivo. Mascitti & Corey discussed this briefly in the paper: “[i]f the biosynthesis were to occur by a cascade-type polycyclization, it would have to be novel in terms of the chemistry used because of the unfavorable energetics and the paucity of the known chemical reactions of this type.” They also said “unraveling the biosynthetic mechanism … [will be] as challenging as the chemical synthesis” – I don’t know about you, but I can hardly wait to read the paper that explores the mechanism of ladderane synthase…

Joshua

Joshua Finkelstein (Associate Editor, Nature)