83522-39-8Relevant articles and documents
Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents
Kuppusamy, Rajesh,Yasir, Muhammad,Berry, Thomas,Cranfield, Charles G.,Nizalapur, Shashidhar,Yee, Eugene,Kimyon, Onder,Taunk, Aditi,Ho, Kitty K.K.,Cornell, Bruce,Manefield, Mike,Willcox, Mark,Black, David StC,Kumar, Naresh
, p. 1702 - 1722 (2018)
Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3′-amino-[1,1′-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.
Catalytic dehydrative peptide synthesis with gem-diboronic acids
Michigami, Kenichi,Sakaguchi, Tatsuhiko,Takemoto, Yoshiji
, p. 683 - 688 (2020/01/02)
Alkane-gem-diboronic acids have emerged as versatile organoboron catalysts for dehydrative amidation of α-Amino acids. A phenol-substituted multiboron catalyst with a B-C-B structure outperformed simple arylboronic acids in the condensation of α-Amino acids with suppressed epimerization of electrophiles. gem-diboronic acid catalysis were compatible with various O, N, and S-functionalized α-Amino acids bearing N-protecting groups including common carbamates used in peptide synthesis (Boc, Cbz, Fmoc). N-Trifluoroacetyl protection enabled an unprecedented catalytic dehydrative peptide synthesis at room temperature. Preliminary mechanistic studies revealed carboxylate-binding nature of gem-diboronic acids, orthogonal to the activation of carboxylic acids by arylboronic acids. The distinctive reactivity of the gem-diboronic acids would open prospects for mild catalytic peptide condensation.
Facile Cu(ii)-mediated conjugation of thioesters and thioacids to peptides and proteins under mild conditions
Sun, Yao,Lyu, Zhenbin,Wang, Zhiqiang,Zeng, Xiaodong,Zhou, Hui,Xu, Fuchun,Chen, Ziyang,Xu, Yuling,Xu, Ping,Hong, Xuechuan
supporting information, p. 3610 - 3614 (2018/05/26)
The bioconjugation of peptide derivatives such as polypeptides, peptide-based probes and proteins is a vibrant area in many scientific fields. However, reports on metal-mediated chemical methods towards native peptides especially non-engineering protein modification under mild conditions are still limited. Herein, we describe a novel Cu(ii)-mediated strategy for the conjugation of thioesters/thioacids to peptides under mild conditions with high functional group tolerance. Based on this strategy, polypeptides, even peptide-based fluorescent probes, can be efficiently constructed. Finally, the selective modification of lysine residues of native Ub with thioesters could be realized and complete conjugation of Ub could be achieved even under equivalent Cu(ii). These promising results could greatly expand Cu(ii)-mediated reaction strategies on chemical biology and molecular imaging.
