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Chemistry 2022 Aug 2. Epub 2022 Aug 2.

Universita degli Studi di Urbino Carlo Bo, Department of Biomolecular Sciences, P.zza Rinascimento 6, 61029, Urbino, ITALY.

The growing importance of structurally diverse and functionalized enantiomerically pure unnatural amino acids in the design of drugs, including peptides, has stimulated the development of new synthetic methods. Herein, we report the challenging direct asymmetric alkylation of cyclic ketones with dehydroalanine derivatives via a conjugate addition reaction for the synthesis of enantiopure ketone-based α-unnatural amino acids. The key to success was the design of a bifunctional primary amine-thiourea catalyst that combines H-bond-directing activation and enamine catalysis. Read More

J Proteomics 2022 Jul 30;267:104686. Epub 2022 Jul 30.

Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, 1000 Skopje, North Macedonia. Electronic address:

Understanding molecular mechanisms that underpin azoospermia and discovery of biomarkers that could enable reliable, non-invasive diagnosis are highly needed. Using label-free data-independent LC-MS/MS acquisition coupled with ion mobility, we compared the FFPE testicular proteome of patients with obstructive (OA) and non-obstructive azoospermia (NOA) subtypes hypospermatogenesis (Hyp) and Sertoli cell-only syndrome (SCO). Out of 2044 proteins identified based on ≥2 peptides, 61 proteins had the power to quantitatively discriminate OA from NOA and 30 to quantitatively discriminate SCO from Hyp and OA. Read More

Commun Biol 2022 Jul 28;5(1):751. Epub 2022 Jul 28.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Read More

Cell Death Dis 2022 Jul 28;13(7):656. Epub 2022 Jul 28.

Soochow University Laboratory of Cancer Molecular Genetics, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, China.

Regulator of G-protein signaling 6 (RGS6) is a newly discovered tumor suppressor that has been shown to be protective in development of various cancers such as breast cancer and bladder cancer. But the mechanisms underlying these tumor-suppressing functions of RGS6 are not fully understood. Here, we discover a novel function of RGS6 in suppressing TGF-β-induced epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells and in vivo NSCLC metastasis. Read More

J Am Soc Mass Spectrom 2022 Jul 26. Epub 2022 Jul 26.

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.

The model nonapeptide AAARAAKAG* (* indicates amide) is used to explore N-C bond fragmentation under CID-MS conditions. Neighboring group participation and the effect of positioning of Lys and Arg residues on N-C bond cleavage is established using a library of synthetic peptide analogues. The importance of the Arg residue at position 4 and the to +3 spacing between Arg and Lys residues in determining the formation of the N-C bond cleaved product ions () is demonstrated by a comparative MS study of positional variants in analogue peptides. Read More