- Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents
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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.
- 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
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Read Online
- Copper-Promoted N-Arylation of the Indole Side Chain of Tryptophan Using Triarylbismuthines
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A simple protocol for the regioselective N-arylation of the indole side chain of tryptophan using triarylbismuth reagents as the arylating agent is reported. The reaction is catalyzed by copper(II) acetate, and operates in the presence of triethylamine or
- Le Roch, Adrien,Chan, Hwai-Chien,Gagnon, Alexandre
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supporting information
p. 5815 - 5819
(2020/07/25)
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- Catalytic dehydrative peptide synthesis with gem-diboronic acids
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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.
- Michigami, Kenichi,Sakaguchi, Tatsuhiko,Takemoto, Yoshiji
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p. 683 - 688
(2020/01/02)
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- MITHRAMYCIN DERIVATIVES HAVING INCREASED SELECTIVITY AND ANTI-CANCER ACTIVITY
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Mithramycin side chain carboxylic acid (MTM-SA) derivative are provided, which include a substituted amino acid derivative, a substituted amino acid dipeptide derivative, or an unsubstituted dipeptide derivative. The MTM-SA derivatives are useful for treatment of cancer or neuro-diseases associated with an aberrant erythroblast transformation-specific transcription factor. Unique MTM-SA derivatives have increased selectively toward ETS transcription factor.
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Paragraph 0095; 0122
(2019/04/05)
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- Facile Cu(ii)-mediated conjugation of thioesters and thioacids to peptides and proteins under mild conditions
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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.
- Sun, Yao,Lyu, Zhenbin,Wang, Zhiqiang,Zeng, Xiaodong,Zhou, Hui,Xu, Fuchun,Chen, Ziyang,Xu, Yuling,Xu, Ping,Hong, Xuechuan
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supporting information
p. 3610 - 3614
(2018/05/26)
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- Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers
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Mithramycin A (1) was identified as the top potential inhibitor of the aberrant ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1 has a narrow therapeutic window, compelling us to seek less toxic and more selective analogues. Here, we used MTMSA (2) to generate analogues via peptide coupling and fragment-based drug development strategies. Cytotoxicity assays in ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and 61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for 1. Importantly, the cytotoxicity of 60 and 61 is 100 nM in ETS cells. Molecular assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1 mediated transcription in Ewing sarcoma. Structural analysis shows that positioning the tryptophan residue in a distal position improves selectivity, presumably via interaction with the ETS transcription factor. Thus, these analogues may present new ways to target transcription factors for clinical use.
- Mitra, Prithiba,Eckenrode, Joseph M.,Mandal, Abhisek,Jha, Amit K.,Salem, Shaimaa M.,Leggas, Markos,Rohr, Jürgen
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p. 8001 - 8016
(2018/09/06)
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- Synthesis and Biological Evaluations of a Series of Thaxtomin Analogues
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Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive struc
- Zhang, Hongbo,Wang, Qingpeng,Ning, Xin,Hang, Hang,Ma, Jing,Yang, Xiande,Lu, Xiaolin,Zhang, Jiabao,Li, Yonghong,Niu, Congwei,Song, Haoran,Wang, Xin,Wang, Peng George
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p. 3734 - 3741
(2015/04/27)
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- Ultrasound-assisted synthesis and biological evaluation of 1,4-benzodioxane-2-carboxyl-amino acids and Peptides
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A series of peptides containing 1,4-benzodioxane nucleus were attempted to synthesize by conventional as well as green techniques like microwave-assisted and sonication, using dicyclohexylcarbodiimide (DCC) as a coupling reagent and triethylamine as a bas
- Malipeddi, Himaja,Gowda, Visruth,Das, Moonjit
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p. 113 - 118
(2019/01/16)
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- A traceless approach to amide and peptide construction from thioacids and dithiocarbamate-terminal amines
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A novel and traceless strategy has been devised that allows a coupling of thioacids and dithiocarbamate-terminal amines. This strategy had been assumed to be dependent on the attachment of a functional equivalent of a cysteine side chain in earlier native chemical ligation approaches. This approach enables the traceless removal of CS2 to directly generate the desired amide bond and is compatible with a range of unprotected side chains of amino acid. The ability to produce amide or peptides by a traceless removal of the auxiliary is a significant virtue of the method. Meanwhile, the application of this new peptide-bond-forming reaction to the synthesis of novel endomorphin (EM) derivatives with various binding potencies was realized.
- Chen, Wenteng,Shao, Jiaan,Hu, Miao,Yu, Wanwan,Giulianotti, Marc A.,Houghten, Richard A.,Yu, Yongping
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p. 970 - 976
(2013/06/05)
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- Novel β-carboline-tripeptide conjugates attenuate mesenteric ischemia/reperfusion injury in the rat
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We have synthesized a series of new β-carboline-tripeptide conjugates, and examined their anti-inflammatory properties in a mouse model of xylene-induced ear edema. The analgesic capacity of these compounds was further evaluated in a rodent tail flick ass
- Bi, Wei,Bi, Yue,Xue, Ping,Zhang, Yanrong,Gao, Xiang,Wang, Zhibo,Li, Meng,Baudy-Floc'H, Michele,Ngerebara, Nathaniel,Li, Xiaoxu,Gibson, K. Michael,Bi, Lanrong
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experimental part
p. 2441 - 2452
(2011/06/21)
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- Antimicrobial activity, biocompatibility and hydrogelation ability of dipeptide-based amphiphiles
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The development of new antibiotics is of increasing importance due to the growing resistance power of microbes against conventional drugs. To this end, cationic peptides are emerging as clinically potent antimicrobial agents. In the present study, we have
- Mitra, Rajendra Narayan,Shome, Anshupriya,Paul, Pritha,Das, Prasanta Kumar
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experimental part
p. 94 - 102
(2009/04/07)
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- Synthesis, characterization and antimicrobial studies on some newer imidazole analogs
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A novel series of 3,5-diiodo-4-(2-methyl-1H-imidazol-5-yl)benzoic acid analogs of amino acids, dipeptides and tripeptides was synthesized by using dicyclohexylcarbodiimide and diisopropylcarbodiimide (DCC/DIPC) as coupling agents and triethylamine (TEA) as base. Structures of all the newly synthesized compounds were confirmed by elemental analysis and IR, 1H NMR, 13C NMR and mass spectral data. Imidazolopeptides were investigated for their antimicrobial activity and some of newly synthesized compounds 2c, 2d, 2h and their hydrolyzed analogs 3b, 3d exhibited potent bioactivity against pathogenic fungi Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii with MIC values of 12.5-6 μg/ml, as compared to the reference drug - griseofulvin. In addition, moderate activity against gram negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae was also observed for synthesized imidazolopeptides. Oesterreichische Apotheker-Verlagsgesellschaft m. b. H.
- Dahiya, Rajiv
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p. 217 - 239
(2008/12/22)
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- Efficient synthesis of 2,5-diketopiperazines using microwave assisted heating
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In this study a general, efficient and environmentally benign solution phase synthesis of 2,5-diketopiperazines (DKPs) using microwave assisted heating in water is described. A series of 11 structurally different DKPs have been synthesized from dipeptide methyl esters. A range of common laboratory solvents have been tested as well as different reaction times and temperatures. Both classic thermal and microwave assisted heating have been investigated. Microwave assisted heating for 10 min using water as solvent proved, by far, to be the most efficient method of cyclization giving moderate to excellent yields (63-97%) of DKPs. In contrast to other published procedures, this method seems independent of the amino acid sequence.
- Tullberg, Marcus,Gr?tli, Morten,Luthman, Kristina
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p. 7484 - 7491
(2007/10/03)
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- (Nitro) hymenamide A, unusual biologically active cyclic peptide
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A new biological active cyclic peptide (Nitro) Hymenamide A has been synthesized and the structure was established on the basis of analytical, IR, NMR and mass spectral data. The new compound was subjected to both antimicrobial and pharmacological studies.
- Belagali,Himaja,Kumar,Thomas,Prakasini,Poojary
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p. 160 - 164
(2007/10/03)
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- Synthetic and biological studies on 5-(p-chlorophenyl)furan-2-carboxyl peptides and 4-[2′-(5′-formyl)furyl]benzoyl peptides
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Substituted anilines are coupled with furoic acid and furfural at the position-5 to get 5-(p-chlorophenyl)furan-2-carboxylic acid and 4-[2′-(5′-formyl) furyl]benzoic acid which on further coupling with amino acid esters, di-, tetra- and hexapeptides yield
- Belagali,Harish Kumar,Boja, Poojary,Himaja
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p. 370 - 375
(2007/10/03)
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- Efficient synthesis of substituted oxopiperazines from amino acids
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The synthesis of substituted oxopiperazines, which may act as conformationally constrained peptide mimics, is reported. The synthesis is based on the cyclization of sulfonamide dipeptides with dibromoethane as the 1,2-dielectrophile. Alternatively, these
- Mohamed, Nazim,Bhatt, Ulhas,Just, George
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p. 8213 - 8216
(2007/10/03)
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