136523-92-7Relevant articles and documents
Activity and Predicted Nephrotoxicity of Synthetic Antibiotics Based on Polymyxin B
Gallardo-Godoy, Alejandra,Muldoon, Craig,Becker, Bernd,Elliott, Alysha G.,Lash, Lawrence H.,Huang, Johnny X.,Butler, Mark S.,Pelingon, Ruby,Kavanagh, Angela M.,Ramu, Soumya,Phetsang, Wanida,Blaskovich, Mark A. T.,Cooper, Matthew A.
, p. 1068 - 1077 (2016)
The polymyxin lipodecapeptides colistin and polymyxin B have become last resort therapies for infections caused by highly drug-resistant Gram-negative bacteria. Unfortunately, their utility is compromised by significant nephrotoxicity and polymyxin-resistant bacterial strains. We have conducted a systematic activity-toxicity investigation by varying eight of the nine polymyxin amino acid free side chains, preparing over 30 analogues using a novel solid-phase synthetic route. Compounds were tested against a panel of Gram-negative bacteria and counter-screened for in vitro cell toxicity. Promising compounds underwent additional testing against primary kidney cells isolated from human kidneys to better predict their nephrotoxic potential. Many of the new compounds possessed equal or better antimicrobial potency compared to polymyxin B, and some were less toxic than polymyxin B and colistin against mammalian HepG2 cells and human primary kidney cells. These initial structure-activity and structure-toxicity studies set the stage for further improvements to the polymyxin class of antibiotics.
Solid-phase total synthesis and structure proof of callipeltin B
Krishnamoorthy, Ravi,Vazquez-Serrano, Leslie D.,Turk, Jeffrey A.,Kowalski, Jennifer A.,Benson, Alan G.,Breaux, Nneka T.,Lipton, Mark A.
, p. 15392 - 15393 (2006)
The cytotoxic, cyclic heptadepsipeptide, natural product callipeltin B was synthesized on a solid-phase support in 15% overall yield. Comparison of the 1H NMR spectra of three synthetic isomers with those of callipeltin B confirmed the configurational reassignment of its threonine residues as d-allothreonine and the assignment of the configuration of its β-methoxytyrosine residue as (2R,3R). Copyright
METHOD OF PREPARING GLYCOPEPTIDES
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Paragraph 0127, (2016/08/29)
A method is provided for the synthesis of glycopeptides using a sugar assisted ligation strategy, wherein an N-terminal peptide portion in the form of a thioester is coopled with a C-terminal peptide portion bearing a carbohydrate moiety comprising a thiol group.
Solid-phase parallel synthesis of functionalised medium-to-large cyclic peptidomimetics through three-component coupling driven by aziridine aldehyde dimers
Treder, Adam P.,Hickey, Jennifer L.,Tremblay, Marie-Claude J.,Zaretsky, Serge,Scully, Conor C. G.,Mancuso, John,Doucet, Annie,Yudin, Andrei K.,Marsault, Eric
, p. 9249 - 9255 (2015/06/16)
The first solid-phase parallel synthesis of macrocyclic peptides using three-component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9- to 18-membered aziridine-containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides. Solid-phase macrocycles: The first solid-phase parallel synthesis of macrocyclic peptides using three-component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9- to 18-membered aziridine-containing macrocycles, which are then functionalised by nucleophilic opening of the aziridine ring (see scheme). This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.
Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and TN antigen via nickel catalysis
Yu, Fei,McConnell, Matthew S.,Nguyen, Hien M.
supporting information, p. 2018 - 2021 (2015/04/27)
The highly α-selective and scalable synthesis of the Fmoc-protected GalNAc-threonine amino acid and TN antigen in gram scale (0.5-1 g) is described. The challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of threonine residues with C(2)-N-ortho-(trifluoromethyl)benzylidenamino trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2-amino glycoside was obtained in 66% yield (3.77 g) with α-only selectivity and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN antigen. This operationally simple procedure no longer requires utilization of the commonly used C(2)-azido donors and overcomes many of the limitations associated with the synthesis of 1,2-cis linkage.
Synthesis of an isotopically-labelled antarctic fish antifreeze glycoprotein probe
Wojnar, Joanna M.,Evans, Clive W.,Devries, Arthur L.,Brimble, Margaret A.
, p. 723 - 731 (2012/07/14)
Antifreeze glycoproteins (AFGPs) are glycosylated polypeptides produced by Antarctic and Arctic fishes, which allow them to survive in seawater at sub-zero temperatures. An investigation into the postulated enteric uptake of AFGP synthesized in the exocrine pancreas of Antarctic fishes required a custom-prepared AFGP probe that incorporated seven isotopically-labelled Ala residues for detection by mass spectrometry. The AFGPs are composed of a repetitive three amino acid unit (Ala-Ala-Thr), in which the threonine residue is glycosylated with the disaccharide β-d-Gal-(1→3) α-d-GalNAc. The synthesis of isotopically-labelled AFGP8 (1), as well as the optimized synthesis of the protected glycosylated amino acid building block 2, is reported.
Alcohols immobilization onto 2-chlorotritylchloride resin under microwave irradiation
Rizzi, Luca,Cendic, Katarina,Vaiana, Nadia,Romeo, Sergio
supporting information; experimental part, p. 2808 - 2811 (2011/06/19)
The immobilization of alcohols onto 2-chlorotritylchloride resin using microwave irradiation was studied. Three different Fmoc-aminoalcohols were tested: the phenol-like Fmoc-tyramine, the primary alcohol Fmoc-ethanolamine, and the secondary alcohol Fmoc-
Sequential activation and deactivation of protein function using spectrally differentiated caged phosphoamino acids
Goguen, Brenda N.,Aemissegger, Andreas,Imperiali, Barbara
supporting information; experimental part, p. 11038 - 11041 (2011/09/14)
Photolabile caging groups, including the 1-(2-nitrophenyl)ethyl (NPE) group, have been applied to probe many biological processes, including protein phosphorylation. Although studies with NPE-caged phosphoamino acids have provided valuable information, these investigations have been limited to the use of only one caged species in a single experiment. To expand the scope of these tools, we have developed an approach for sequentially uncaging two different phosphopeptides in one system, enabling interrogation of multiple phosphorylation events. We present the synthesis of [7-(diethylamino)coumarin-4- yl]methyl (DEACM)-caged phosphorylated serine, threonine, and tyrosine building blocks for Fmoc-based solid-phase peptide synthesis to allow convenient incorporation of these residues into peptides and proteins. Exposure of DEACM- and NPE-caged phosphopeptides to 420 nm light selectively releases the DEACM group without affecting the NPE-caged peptide. This then enables a subsequent irradiation event at 365 nm to remove the NPE group and liberate a second phosphopeptide. We demonstrate the versatility of this general sequential uncaging approach by applying it to control Wip1 phosphatase with two wavelengths of light.
Amino acid building blocks for efficient Fmoc solid-phase synthesis of peptides adenylylated at serine or threonine
Albers, Michael F.,Van Vliet, Bart,Hedberg, Christian
supporting information; experimental part, p. 6014 - 6017 (2011/12/15)
The first straightforward building block based (non-interassembly) synthesis of peptides containing adenylylated serine and threonine residues is described. Key features include final global acidolytic protective group removal as well as full compatibility with standard Fmoc solid-phase peptide synthesis (SPPS). The described Thr-AMP SPPS-building block has been employed in the synthesis of the Thr-adenylylated sequence of human GTPase CDC42 (Ac-SEYVP-T(AMP)-VFDNYGC-NH2). Further, we demonstrate proof-of-concept for the synthesis of an Ser-adenylylated peptide (Ac-GSGA-S(AMP)-AGSGC-NH2) from the corresponding adenylylated serine building block.
Microwave-assisted synthesis of fluorescein-labelled GalNAcα1-O-Ser/ Thr (Tn) glycopeptides as immunological probes
Lee, Dong Jun,Harris, Paul W.R.,Kowalczyk, Renata,Dunbar, P. Rod,Brimble, Margaret A.
body text, p. 763 - 769 (2010/10/01)
Fluorescently labelled glycopeptides containing GalNAcα1-O-Ser/Thr residues provide valuable immunological probes for the development of cancer vaccines. The microwave-assisted automated Fmoc solid-phase synthesis of a series of 5(6)-carboxyfluorescein-labelled GalNAcα1-O-Ser/Thr peptides is described. Lys(Dde)-Gly-Wang polystyrene resin was elongated using Fmoc SPPS with incorporation of several GalNAcα1-O-Ser/Thr residues. Deprotection of the Lys(Dde) then allowed attachment of the 5(6)-carboxyfluorescein label. The synthetic methodology described is flexible and suitably robust enabling the incorporation of three contiguous GalNAcα1-O-Ser residues into the peptide chain. Georg Thieme Verlag Stuttgart · New York.
