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2022 ◽  
Vol 238 ◽  
pp. 111976
Yan Zhang ◽  
Chuangchuang Cao ◽  
Bowen Mei ◽  
Jiabiao Zou ◽  
Long Zhao ◽  

2022 ◽  
Vol 194 ◽  
pp. 113045
Mengyi Deng ◽  
Xia Chen ◽  
Yuben Qiao ◽  
Zhengyi Shi ◽  
Jianping Wang ◽  

2022 ◽  
Vol 370 ◽  
pp. 130962
Yanzhao Liu ◽  
Jihong Liu ◽  
Gongji Liu ◽  
Ruibing Duan ◽  
Yangyang Sun ◽  

Benjamin J. Lethbridge ◽  
Robert E. Asenstorfer ◽  
Laura S. Bailey ◽  
Brenda T. Breil ◽  
Jodie V. Johnson ◽  

AbstractTrifolitoxin (TFX, C41H63N15O15S) is a selective, ribosomally-synthesized, post-translationally modified, peptide antibiotic, produced by Rhizobium leguminosarum bv. trifolii T24. TFX specifically inhibits α-proteobacteria, including the plant symbiont Rhizobium spp., the plant pathogen Agrobacterium spp. and the animal pathogen Brucella abortus. TFX-producing strains prevent legume root nodulation by TFX-sensitive rhizobia. TFX has been isolated as a pair of geometric isomers, TFX1 and TFX2, which are derived from the biologically inactive primary amino acid sequence: Asp-Ile-Gly-Gly-Ser-Arg-Gln-Gly-Cys-Val-Ala. Gly-Cys is present as a thiazoline ring and the Arg-Gln-Gly sequence is extensively modified to a UV absorbing, blue fluorescent chromophore. The chromophore consists of a conjugated, 5-membered heterocyclic ring and side chain of modified glutamine.

Jun Takeuchi ◽  
Saya Mimura ◽  
Toshiyuki Ohnishi ◽  
Yasushi Todoroki

2022 ◽  
Vol 9 ◽  
Tamara Matthyssen ◽  
Wenyi Li ◽  
James A. Holden ◽  
Jason C. Lenzo ◽  
Sara Hadjigol ◽  

Antimicrobial peptides (AMPs) are found in nearly all living organisms, show broad spectrum antibacterial activity, and can modulate the immune system. Furthermore, they have a very low level of resistance induction in bacteria, which makes them an ideal target for drug development and for targeting multi-drug resistant bacteria ‘Superbugs’. Despite this promise, AMP therapeutic use is hampered as typically they are toxic to mammalian cells, less active under physiological conditions and are susceptible to proteolytic degradation. Research has focused on addressing these limitations by modifying natural AMP sequences by including e.g., d-amino acids and N-terminal and amino acid side chain modifications to alter structure, hydrophobicity, amphipathicity, and charge of the AMP to improve antimicrobial activity and specificity and at the same time reduce mammalian cell toxicity. Recently, multimerisation (dimers, oligomer conjugates, dendrimers, polymers and self-assembly) of natural and modified AMPs has further been used to address these limitations and has created compounds that have improved activity and biocompatibility compared to their linear counterparts. This review investigates how modifying and multimerising AMPs impacts their activity against bacteria in planktonic and biofilm states of growth.

2022 ◽  
Jaru Taechalertpaisarn ◽  
Satoshi Ono ◽  
Okimasa Okada ◽  
Timothy C. Johnstone ◽  
R. Scott Lokey

Despite the notoriously poor membrane permeability of peptides in general, many cyclic peptide natural products show high passive membrane permeability and potently inhibit a variety of “undruggable” intracellular targets. A major impediment to designing cyclic peptides with good permeability is the high desolvation energy associated with the peptide backbone amide NH groups. Strategies for mitigating the deleterious effect of the backbone NH group on permeability include N-methylation, steric occlusion, and the formation of intramolecular hydrogen bonds with backbone carbonyl oxygens, while there have been relatively few studies on the use of polar side chains to sequester backbone NH groups. We investigated the ability of N,N-pyrrolidinyl glutamine (Pye), whose side chain contains a powerful hydrogen bond accepting C=O amide group but no hydrogen bond donors, to sequester exposed backbone NH groups in a series of cyclic hexapeptide diastereomers. Analyses of partition coefficients, lipophilic permeability efficiencies (LPE), artificial and cell-based permeability assays revealed that specific Leu-to-Pye substitutions conferred dramatic improvements in aqueous solubility and permeability in a scaffold- and position-dependent manner. Introduction of the Pye residue thus offers a complementary tool, alongside traditional approaches, for improving membrane permeability and solubility in cyclic peptides.

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