LongLarf

Publication date: 13 April 2023

Source: Chem, Volume 9, Issue 4

Author(s): Nupur Goswami, Soumya Kumar Sinha, Partha Mondal, S. Adhya, Ayan Datta, Debabrata Maiti

Nature Catalysis, Published online: 13 February 2023; doi:10.1038/s41929-023-00914-7

Hydrofunctionalization of α-olefins with mineral acids usually proceeds with Markovnikov selectivity. Now, a strategy based on synergistic phase transfer and photoredox catalysis is developed to facilitate anti-Markovnikov addition of aqueous hydrochloric and nitric acid to unactivated alkenes.

Science, Volume 379, Issue 6631, Page 484-488, February 2023.

Nature Catalysis, Published online: 28 December 2022; doi:10.1038/s41929-022-00889-x

Biocatalytic methods to access thioesters, such as acyl-coenzyme A, from carboxylic acids are underdeveloped. Now, it is shown that the adenylation domain of a carboxylic acid reductase enzyme can be exploited as a promiscuous thioester synthetase and combination with acyltransferases facilitates the synthesis of amides and peptide labelling.

Nature Catalysis, Published online: 19 January 2023; doi:10.1038/s41929-022-00908-x

The design of complementary catalysts to target different C–H bonds in a specific molecule is challenging. Now, a pair of P450-based carbene transferase enzymes is engineered, which can selectively cyanomethylate either a C(sp3)–H or arene C(sp2)–H bond present in the same substrate.

Stoichiometric intermolecular OPA-amine-thiol three-component reaction were realized through the use of a guanidine additive. This method enables the construction of peptide-peptide and peptide-drug conjugates in a modular fashion, and it is anticipated that it will open up new and diverse opportunities to access new conjugate structures for chemical biology, medicinal chemistry and drug discovery.

Abstract

Recently, ortho-phthalaldehyde (OPA) is experiencing a renascence for the modification of proteins and peptides through OPA-amine two-component reactions for bioconjugation and intramolecular OPA-amine-thiol three-component reactions for cyclization. Historically, small thiol molecules were used in large excess to allow for the intermolecular OPA-amine-thiol reaction forming 1-thio-isoindole derivatives. In this study, we discovered that guanidine could serve as an effective additive to switch the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process and enable the modular construction of peptide-peptide, and peptide-drug conjugate structures. Thus, 12 model peptide-peptide conjugates have been synthesized from unprotected peptides featuring all proteinogenic residues. Besides, 6 peptide-drug conjugates have been prepared in one step, with excellent conversions and isolated yields. In addition, a conjugate product has been further functionalized by utilizing a premodified OPA derivative, demonstrating the versatility and flexibility of this reaction.