In-silico assessment of novel peptidomimetics inhibitor targeting STAT3 and STAT4 N-terminal domain dimerization: A comprehensive study using molecular docking, molecular dynamics simulation, and binding free energy analysis.

Dysregulation in Janus kinase-Signal Transducer and Activation of Transcription (JAK-STAT) pathway is closely linked to various cancer types. The N-terminal domain (NTD) of STAT proteins, upon dimerization, assumes a multifaceted role with remarkable adaptability in mediating interactions between proteins. Consequently, the strategic targeting of the N-terminal domain of STATs has emerged as a promising tactic for disrupting dimerization and impeding the translocation of STAT proteins.

H, N and C resonance backbone and side-chain assignments and secondary structure determination of the BRCT domain of Mtb LigA.

The BRCA1 carboxyl-terminal (BRCT) domain, an evolutionarily conserved structural motif, is ubiquitous in a multitude of proteins spanning prokaryotic and eukaryotic organisms. In Mycobacterium tuberculosis (Mtb), BRCT domain plays a pivotal role in the catalytic activity of the NAD+-dependent DNA ligase (LigA). LigA is pivotal in DNA replication, catalyzing the formation of phosphodiester bonds in Okazaki fragments and repairing single-strand breaks in damaged DNA, essential for the survival of Mtb.

Diastereoselective [3 + 2] Cycloaddition of Quinoxalin-2(1)-ones with Donor-Acceptor Cyclopropanes: Efficient Synthesis of Tetrahydro pyrrolo[1,2-]quinoxalin-4(5)-ones.

A ytterbium triflate-catalyzed diastereoselective [3 + 2] cycloaddition of quinoxalinones with donor-acceptor cyclopropanes and cyclobutanes is described. A series of tetrahydropyrrolo-quinoxalinone derivatives were obtained in high yields (up to 96%) with excellent diastereoselectivities (up to 46:1). Other medicinally important heterocycles like benzoxazinone, isoquinoxalinone, and dibenzoxazepine derivatives were also suitable for the desired annulation reaction.

Conformation Analysis of GalNAc-Appended Sugar Amino Acid Foldamers as Glycopeptide Mimics.

Sugar amino acid (SAA)-based foldamers with well-defined secondary structures were appended with N-acetylgalactosamine (GalNAc) sugars to access sequence-defined, multidentate glycoconjugates with full control over number, spacing and position. Conformation analysis of these glycopeptides by extensive NMR spectroscopic studies revealed that the appended GalNAc units had a profound influence on the native conformational behaviour of the SAA foldamers. Whereas the 2,5-cis glycoconjugate showed a helical structure in water, comprising of two consecutive 16-membered hydrogen bonds, its 2,5-trans congener displayed an unprecedented 16/10-mixed turn structure not seen before in any glycopeptide foldamer.