Single Amine or Guanidine Modification on Norvancomycin and Vancomycin to Overcome Multidrug-Resistance through Augmented Lipid II Binding and Increased Membrane Activity.

Vancomycin and norvancomycin have diminished antibacterial efficacy due to acquired or intrinsic resistance from mutations in the terminal dipeptide of lipid II in Gram-positive bacteria or failure to penetrate into the periplasm in Gram-negative bacteria. Herein, we rationally designed and synthesized a series of vancomycin analogues bearing single amine or guanidine functionality, altering various linkers and modification sites, to combat the resistance. Extensive antibacterial screening was performed to delineate a comprehensive SAR.

Advances in MiRNAs Involved in Endometrial Carcinoma.

Endometrial carcinoma (EC) is a common malignancy worldwide. Existing evidence has revealed that EC could be associated with abnormal gene expression. Meantime, evidence supports that miRNAs act as critical regulators in gene expression through the binding to the 3'- untranslated region (3'-UTR).

Site- and Stereoselective Glycomodification of Biomolecules through Carbohydrate-Promoted Pictet-Spengler Reaction.

Carbohydrates play pivotal roles in an array of essential biological processes and are consequently involved in many diseases. To meet the needs of glycobiology research, chemical enzymatic and non-enzymatic methods have been developed to generate glycoconjugates with well-defined structures. Herein, harnessing the unique properties of C6-oxidized glycans, we report a straightforward and robust strategy for site- and stereoselective glycomodification of biomolecules with N-terminal tryptophan residues by a carbohydrate-promoted Pictet-Spengler reaction, which is not adapted to typical aldehyde substrates under biocompatible conditions.

Recent advances in antibody glycoengineering for the gain of functions.

Glycans play important roles in antibody functions, and antibody glycoengineering has long been an important research field. Here, we summarize the significant strategies of antibody glycoengineering, including expressed antibody glycoengineering in mammalian cell expression systems, chemo-enzymatic antibody glycoengineering, and yeast expression system-based antibody engineering, as well as the applications of glycoengineering in antibody-drug conjugates. These advances in antibody glycoengineering will provide a comprehensive understanding and inspire us to develop more advanced techniques to achieve glycoengineered antibodies.

Enhanced antibody-defucosylation capability of α-L-fucosidase by proximity-based protein fusion.

Up to date, the reported fucosidases generally show poor activities toward the IgG core-fucose, which limits the efficiency of ENGase-catalyzed glycoengineering process. However, EndoS or EndoS2 owns excellent activity and great selectivity towards the N-glycosylation of IgGs, and their non-catalytic domains are deduced to have specific interactions to IgG Fc domain that result in the great activity and selectivity. Herein, we constructed a series fusion protein of AlfC (an α-l-fucosidase from Lactobacillus casei BL23) with EndoS/S2 non-catalytic domain by replacing the catalytic GH (glycan hydrolase) domain of EndoS/S2 with the AlfC.

Association of the PROGINS PgR polymorphism with susceptibility to female reproductive cancer: A meta-analysis of 30 studies.

Aims: The progesterone response of the nuclear progesterone receptor plays an important role in the female reproductive system. Changes in the function of the progesterone receptor gene may increase the risk of reproductive cancer. The present study performed a meta-analysis to examine whether the progesterone receptor gene PROGINS polymorphism was a susceptibility factor for female reproductive cancer.

Correction: Enhanced transglycosylation activity of an Endo-F3 mutant by ligand-directed localization.

Correction for 'Enhanced transglycosylation activity of an Endo-F3 mutant by ligand-directed localization' by Xiangman Zou , , 2022, , 3086-3095, https://doi.org/10.1039/D2OB00030J.

Enhanced transglycosylation activity of an Endo-F3 mutant by ligand-directed localization.

At present, numerous studies have been reported to remodel the -glycans of therapeutic antibodies for the gain of functions. Among the ways of remodeling antibody -glycans, the chemoenzymatic glycoengineering approach by endoglycosidase (ENGase) has been deeply investigated and provided a significant tool for IgG glycoengineering. Among these cases, the transglycosylation activity of Endo-F3, compared to Endo-S and S2, is insufficient and limits its power in remodeling IgG glycosylation.

Design, synthesis, and antibacterial evaluation of vancomycin-LPS binding peptide conjugates.

Developing novel antibiotics is urgently needed with emergency of drug resistance. Vancomycin, the last resort for intractable Gram-positive bacterial infections, is ineffective against Gram-negative bacteria and vancomycin resistant bacteria. Herein, we report a series of novel vancomycin derivatives carrying LPS binding peptides, vancomycin-LPS binding peptide conjugates (VPCs).

A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide.

Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains.

A novel genotyping technique for discriminating LVAS-associated high-frequency variants in SLC26A4 gene.

An increasing number of biological and epidemiological evidence suggests that c.919-2A > G and c.2168A > G variants of solute carrier family 26, member 4 (SLC26A4) gene play a critical role in the development of large vestibular aqueduct syndrome (LVAS).