Contemporary Applications of Thioamides and Methods for Their Synthesis

Abstract

Thioamides are naturally occurring isosteres of amide bonds in which the chalcogen atom of the carbonyl is changed from oxygen to sulfur. This substitution gives rise to altered nucleophilicity and hydrogen bonding properties with importance for both chemical reactivity and non‐covalent interactions. As such, thioamides have been introduced into biologically active compounds to achieve improved target affinity and/or stability towards hydrolytic enzymes but have also been applied as probes of protein and peptide folding and dynamics. Recently, a series of new methods have been developed for the synthesis of thioamides as well as their utilization in peptide chemistry. Further, novel strategies for the incorporation of thioamides into proteins have been developed, enabling both structural and functional studies to be performed. In this Review, we highlight the recent developments in the preparation of thioamides and their applications for peptide modification and study of protein function.

Nanoarchitectured Graphene Organic Frameworks with High Iodine Uptake and Antibacterial Activity

“…22,23 Various research studies have demonstrated the potential of compounds containing thioamide-based ligands for various biological applications, particularly their antibacterial properties. 24,25 At the same time, medicinal chemists have used thioamides to improve the pharmacokinetic properties and the thermal and proteolytic stability of compounds containing amide moieties. 24 Pharmaceutical compounds containing the thioamide group, such as drugs for hyperthyroidism (methimazole, methyl-, and propylthiouracil), have been found to react with iodine molecules during a multistep and complex process.…”

“…Organic ligands such as thioamides were deemed synthetic isostere for amides in protein scaffolds and peptides before they were discovered in natural molecules . The strategic incorporation of thioamide into both synthetic and natural compounds has the potential to enable both dramatic and subtle changes in amide interactions due to this single-atom substitution. , Various research studies have demonstrated the potential of compounds containing thioamide-based ligands for various biological applications, particularly their antibacterial properties. , At the same time, medicinal chemists have used thioamides to improve the pharmacokinetic properties and the thermal and proteolytic stability of compounds containing amide moieties . Pharmaceutical compounds containing the thioamide group, such as drugs for hyperthyroidism (methimazole, methyl-, and propylthiouracil), have been found to react with iodine molecules during a multistep and complex process .…”