Reactions: How macrocyclic peptides compare with natural products, how C&EN can cover climate change stewardship, and how business is implicated in chemistry’s poor image.

Letters to the editor

Macrocyclic peptides and natural products

It was wonderful to read drug discoverers’ new appreciation for complex molecules in the June 24, 2024, issue of C&EN (page 20). Several points presented in the paper for pursuing macrocyclic peptides to obtain a perfect fit are the same points natural product researchers have presented over decades! The features in common with many natural products are that (a) large, and more complex molecules could have a better chance to influence protein-protein interactions than smaller molecules; (b) the molecules are stabler, resistant to rapid breakdown, and have greater oral bioavailability than smaller ones; (c) the molecules have a large surface area to recognize larger interacting sites and lower affinity for smaller interaction; and (d) large molecules can penetrate cells.

A point that is not addressed in the article is that larger binding sites could decrease resistance development because point mutations are not sufficient to dislodge these tight binders.

It may be worthwhile to have macrocyclic peptide chemists use artificial intelligence to screen known natural products to derive innovative ideas for tight and specific binders to make undruggable targets druggable. Methods to obtain stereochemical and skeletal rigidity of scaffold structures are points that could be useful.

What is true for macrocyclic peptides is true for natural products, except more so (with apologies to Jacques Monod, “What is true for E. coli is true for the elephant, except more so”).

Prabhavathi Fernandes
Chapel Hill, North Carolina

Involve business, politics, and society in improving chemistry enterprise

Regarding “Chemistry’s Image Is Harming Talent Acquisition” (C&EN, July 1, 2024, page 23), I found it ironic that the woman who shamed the author for being in the chemical industry identified herself as working in finance. From my perspective, much of chemistry’s image problem is the result of decisions made by those in finance and business. Deferring maintenance is a business decision that has led to chemical releases, fires, contamination, and much pain and suffering. Continuing to make and sell materials long after they are known to be harmful is a business decision aimed at protecting the bottom line, not health. It is a business decision that changes a plant design to prioritize short-term financial gain over long-term energy savings. It is a business decision to put money into advertising recycling symbols knowing that the materials are not recyclable instead of putting that money into finding safer, degradable materials and scalable recycling solutions.

The author is correct that we in the chemistry enterprise must do more to make people aware of the positive aspects of chemistry, but we also need to enlist the help of those in business, politics, and society to change the incentives for making business decisions that lead to terrible long-term outcomes.

Robert Davidson
Denver

Enterprise stewardship for climate change

I have written letters to the editor before about enterprise stewardship. Again with US national elections looming and gridlock in Congress, corporations must take the lead to mitigate and remediate climate change.

Large corporations like Walmart practice stewardship, but it will take more large corporations joining forces to solve climate-related problems.

I would like to see Chemical & Engineering News do an entire issue on enterprise stewardship, reaching out to the large corporations of the world, including in the US, and challenging them—rather than government or countries—to create the path for global climate mitigation and eventual remediation.

Martha Dibblee
Portland, Oregon