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Protective Effects of Alpha-Pinene Pre-Treatment in Renal Ischemia-Reperfusion Injury in Male Rats.
Iran J Kidney Dis
December 2024
Pathology Department, Afzalipour Kerman University of Medical Sciences, Kerman, Iran.
Introduction: Ischemia followed by reperfusion in organ transplantations can lead to ischemia-reperfusion (I-R) injury, which is associated with oxidative stress and inflammatory responses. Alpha-pinene is an organic terpene with well-known antioxidant, anti-inflammatory, and anti-apoptotic properties. This study examines the preventive effects of alpha-pinene against renal I-R-induced kidney dysfunction, oxidative and inflammatory status, apoptosis, and histopathology changes.
View Article and Find Full Text PDFHighly Efficient Transpeptidase-Catalyzed Isopeptide Ligation.
J Am Chem Soc
December 2024
Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland 4072, Australia.
Transpeptidases are specialized enzymes that have evolved for site-selective modification of peptides and proteins at their backbone termini. Approaches for adapting transpeptidases to catalyze side chain modifications are substantially more restricted, and typically rely on large recognition tags or require specific reaction conditions that are not easily compatible with broader applications. Here we show that the engineered asparaginyl ligase AEP1 catalyzes direct isopeptide ligation by accepting an internal 2,3-diaminopropionic acid (Dap) residue adjacent to Leu, a motif that mimics the canonical N-terminal Gly-Leu substrate.
View Article and Find Full Text PDFLate-Stage Reshaping of Phage-Displayed Libraries to Macrocyclic and Bicyclic Landscapes using a Multipurpose Linchpin.
J Am Chem Soc
December 2024
Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Genetically encoded libraries (GEL) are increasingly being used for the discovery of ligands for "undruggable" targets that cannot be addressed with small molecules. Foundational GEL platforms like phage-, yeast-, ribosome-, and mRNA-display have enabled the display of libraries composed of 20 natural amino acids (20AA). Unnatural amino acids (UAA) and chemical post-translational modification (cPTM) expanded GEL beyond the 20AA space to yield unnatural linear, cyclic, and bicyclic peptides.
View Article and Find Full Text PDFCDC20-Mediated Selective Autophagy Degradation of PBRM1 Affects Immunotherapy for Renal Cell Carcinoma.
Adv Sci (Weinh)
December 2024
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P. R. China.
Polybromo 1 (PBRM1) inactivating mutations are associated with clinical benefit from immune checkpoint inhibitor treatments in clear cell renal cell carcinoma (ccRCC). However, whether targeting PBRM1 has the potential to enhance immunotherapy efficacy in patients with wild-type PBRM1 and the upstream pathways that regulate PBRM1 protein stability remain unclear. Here, it is demonstrated that PBRM1 knockdown induced M1 macrophage polarization and infiltration, which enhanced the efficacy of anti-PD-1 immunotherapy in RCC.
View Article and Find Full Text PDFDeciphering the Comprehensive Structure-Activity Relationship of Sunshinamide for Breast Cancer Therapy through Dual Modulation of Apoptotic and Ferroptotic Pathways via TrxR1 and Gpx4 Inhibition.
J Med Chem
December 2024
School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
Sunshinamide, a cyclodepsipeptide, has demonstrated significant potential in inhibiting cancer cell proliferation. Our prior research established the total synthesis and anticancer properties of sunshinamide. However, a deeper understanding of the structure-activity relationship (SAR) of sunshinamide remained imperative.
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