@article{thuan_koirala_pirez_ohata_2025, title={Prebiotic Roles of Formaldehyde as an Activating Agent and a Building Block in Solid-State Peptide Modification}, volume={9}, url={https://doi.org/10.1021/acsbiomedchemau.5c00167}, DOI={10.1021/acsbiomedchemau.5c00167}, abstractNote={Signal transduction by gaseous small molecules is an essential process in modern living systems, where the gasotransmitters relay cellular signals to bio-(macro)-molecules through covalent bond formation. However, the origin or a primordial version of such signaling events in abiotic worlds has been poorly understood to date. Through examination of chemical reactivities between formaldehyde and cyclic dipeptide/diketopiperazine derivatives in prebiotically relevant solid-state environments, this study demonstrates that the gaseous small molecule may serve not only as a mere building block for the abiotic construction of biomolecules but also as an activating agent that transforms the inert peptide into reactive, prebiotically important chemical species. In addition, superiority of solid-state reactions or mechanochemistry to solution-based reaction conditions described in this article may be an indication of potential significance of the mechanical force-induced chemistry for chemical evolution, in particular for abiotic emergence of polypeptides.}, journal={ACS Bio & Med Chem Au}, author={Thuan, Jamie C. and Koirala, Anuja and Pirez, James and Ohata, Jun}, year={2025}, month={Sep} }
 @article{uzoewulu_joyner_thuan_rose_colella_nizam_ishizawa_meguro_enomoto_ohata_2025, title={Tryptophan Bioconjugation through Auxiliary Boron-Accelerated, Additive-Free Friedel–Crafts Alkylation}, volume={12}, url={https://doi.org/10.1021/jacsau.5c01168}, DOI={10.1021/jacsau.5c01168}, abstractNote={Chemical tools have allowed the interrogation of molecular events in biological systems through the realization of additive-free labeling approaches such as strain-promoted chemistry. Although design and synthesis of strained compounds remain challenging tasks, efforts to identify an alternative chemical strategy to achieve such additive-free labeling are lacking. Serendipitously, we found that a trifluoroborate unit can act as an auxiliary group to enable the additive-free Friedel-Crafts alkylation reaction at room temperature in the potentially protein-compatible solvent hexafluoroisopropanol (HFIP) without any additional catalysts such as a Lewis acidic metal and a Brønsted acid. The structure-reactivity relationship of a set of thiophene electrophiles for the dehydrative alkylation of tryptophan revealed the inability of various functional groups to cause such an additive-free labeling process, while all of the synthesized trifluoroborate variants displayed substantially enhanced reactivity even in the absence of additives. As the boron moiety serving as an auxiliary group remains on the thiophene unit after the tryptophan bioconjugation, facile secondary functionalization of alkylated tryptophan through boron-based chemistry proved to be possible at a protein level. Because strain-promoted chemistry has shown great promise for diverse applications beyond small-molecule studies by eliminating the need for additives/catalysts, the boron auxiliary approach may be a promising chemical strategy in a wide variety of contexts.}, journal={JACS Au}, author={Uzoewulu, Chiamaka P. and Joyner, Emily C. and Thuan, Jamie C. and Rose, Kathryn and Colella, Brandon M. and Nizam, Zeinab M. and Ishizawa, Seiya and Meguro, Yasuhiro and Enomoto, Masaru and Ohata, Jun}, year={2025}, month={Dec} }