- Tetrafluoroaryl azide as an N-Terminal capping group for click-To-dissolve diphenylalanine hydrogels
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The synthesis of a bioorthogonal-responsive low molecular weight diphenylalanine (PhePhe)-based hydrogel that is capped with a 4-Azido-2,3,5,6-Tetrafluorobenzyl carbamate self-immolative linker is reported. The hydrogelator (AzF4-PhePhe) generates a stable hydrogel at 0.1 wt%, and rapidly reacts with the bioorthogonal reagent trans-cyclooctene (TCO), inducing a gel-To-solution transition. The critical gel concentration is five-fold lower than our previously synthesized non-fluorinated hydrogelator (Az-PhePhe), and the minimum concentration of TCO required for visible gel-To-solution transition in 24 hours is 1 mM. Doxorubicin can be encapsulated in the hydrogel and TCO-Triggered dissolution results in 76% and 89% release after 10 and 24 hours, respectively. Compared with our non-substituted aryl azide capping group used for Az-PhePhe, the tetrafluorinated aryl azide group improves the stability of the hydrogel in unbuffered water at a lower critical gel concentration, while improving sensitivity towards the bioorthogonal reagent TCO.
- Dadhwal, Sumit,Fairhall, Jessica M.,Gamble, Allan B.,Hook, Sarah
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p. 9234 - 9244
(2020/03/19)
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- One-pot, two-step synthesis of unnatural α-amino acids involving the exhaustive aerobic oxidation of 1,2-diols
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Herein, we report the nor-AZADO-catalyzed exhaustive aerobic oxidations of 1,2-diols to α-keto acids. Combining oxidation with transamination using dl-2-phenylglycine led to the synthesis of free α-amino acids (AAs) in one pot. This method enables the rapid and flexible preparation of a variety of valuable unnatural AAs, such as fluorescent AAs, photoactivatable AAs, and other functional AAs for bioorthogonal reactions.
- Inada, Haruki,Furukawa, Keisuke,Shibuya, Masatoshi,Yamamoto, Yoshihiko
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supporting information
p. 15105 - 15108
(2019/12/26)
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- Mechanistic Evaluation of Bioorthogonal Decaging with trans-Cyclooctene: The Effect of Fluorine Substituents on Aryl Azide Reactivity and Decaging from the 1,2,3-Triazoline
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Bioorthogonal prodrug activation/decaging strategies need to be selective, rapid and release the drug from the masking group upon activation. The rates of the 1,3-dipolar cycloaddition between a trans-cyclooctene (TCO) and a series of fluorine-substituted
- Matikonda, Siddharth S.,Fairhall, Jessica M.,Fiedler, Franziska,Sanhajariya, Suchaya,Tucker, Robert A. J.,Hook, Sarah,Garden, Anna L.,Gamble, Allan B.
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p. 324 - 334
(2018/02/28)
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- Design and synthesis of peptide conjugates of phosphoramide mustard as prodrugs activated by prostate-specific antigen
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A series of Glutaryl-Hyp-Ala-Ser-Chg-Gln-4-aminobenzyl phosphoramide mustard conjugates (1a-e) was designed and synthesized as potential prodrugs for site-specific activation by PSA in prostate cancer cells. All conjugates were found to be substrates of PSA with cleavage occurring between Gln and the para-aminobenzyl (PAB) linker. Structure-activity relationship studies on these conjugates indicated that introduction of electron-withdrawing fluorine(s) on the phenyl ring in the PAB linker uniformly improved the chemical stability of the conjugates while the position of substitution affected differently the self-immolative process of conjugates upon proteolysis. Introduction of a fluorine at ortho position to benzylic phosphoramide as in 1b results in better stability of the conjugate prior to activation while maintaining its antiproliferative activity upon activation by PSA. The conjugate 1b with 2-fluoro substitution was identified as a promising lead for further evaluation and optimization in the development of prostate cancer-targeted prodrugs.
- Wu, Xinghua,Hu, Longqin
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p. 2697 - 2706
(2016/06/08)
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- Photoactivatable phospholipids bearing tetrafluorophenylazido chromophores exhibit unprecedented protonation-state-dependent 19F NMR signals
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Phospholipids bearing tetrafluorophenylazido chromophores were synthesized with perfectly conserved amphiphilicity and photochemical activity. Interestingly however, those phospholipids harboring the amine-linked chromophores exhibited unusual 19/su
- Xia, Yi,Qu, Fanqi,Maggiani, Alain,Sengupta, Kheya,Liu, Cheng,Peng, Ling
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supporting information; experimental part
p. 4248 - 4251
(2011/10/08)
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- Synthesis and pharmacological evaluation of fluorescent and photoactivatable analogues of antiplasmodial naphthylisoquinolines
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The naphthylisoquinoline (NIQ) alkaloids from tropical Ancistrocladaceae and Dioncophyllaceae plants show high antiplasmodial activities in vitro and in vivo, even against chloroquine-resistant strains of the malaria pathogen. For the directed optimization of these activities, an investigation of the mode of action seems most rewarding. We have therefore embarked on the identification of the respective target protein in Plasmodium falciparum. For this purpose, we have developed a flexible pathway for the synthesis of a chemically divergent series of photoactive and fluorescent derivatives of such alkaloids and succeeded in preparing the first functionalized NIQ derivatives, 10, 12, and 35, suited for fluorescence and photoaffinity labeling experiments. Pharmacological investigations ensured that the modified alkaloid derivatives retained their antiplasmodial activity. The work may pave the way for a further improvement of the activity of these natural products and will thus increase their pharmacological potential as a valuable lead structure against the widespread tropical disease malaria.
- Bringmann, Gerhard,Gampe, Christian M.,Reichert, Yanina,Bruhn, Torsten,Faber, Johan H.,Mikyna, Martin,Reichert, Matthias,Leippe, Matthias,Brun, Reto,Gelhaus, Christoph
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p. 6104 - 6115
(2008/09/16)
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- Synthesis of photoactive α-mannosides and mannosyl peptides and their evaluation for lectin labeling
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Adhesion to the glycosylated surface of eukaryotic cells, mediated by lectins for example, plays an important role in inflammation and other cellular processes of living organisms. To elucidate the mechanisms involved in the adhesion to cell surfaces and
- Wiegand, Michaela,Lindhorst, Thisbe K.
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p. 4841 - 4851
(2007/10/03)
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- Ginkgolide derivatives for photolabeling studies: Preparation and pharmacological evaluation
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The terpene trilactones (TTLs), ginkgolides and bilobalide, are structurally unique constituents of Ginkgo biloba extracts, which exhibit various neuromodulatory properties. Although the TTLs are believed to be responsible for some of these effects, the s
- Str?mgaard, Kristian,Saito, D. Roland,Shindou, Hideo,Ishii, Satoshi,Shimizu, Takao,Nakanishi, Koji
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p. 4038 - 4046
(2007/10/03)
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- New Reagents for Photoaffinity Labeling: Synthesis and Photolysis of Functionalized Perfluorophenyl Azides
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Functionalized perfluorophenyl azides (PFPA) 2-6, 8-12, 14-19, and 21-29 were synthesized, allowing the attachment of PFPA to other molecules for application as photolabels.Two biactive molecules were modified by a PFPA as potential photoaffinity labeling reagents.Photolysis of two representative members was investigated.Photolysis of azide 4 in cyclohexane gave 57 percent of CH insertion product.When photolysis was carried out in the presence of diethylamine as a trapping reagent, it gave 65 percent of NH insertion product, and no ring expansion product was found.The nitro azide 19 showed a shoulder absorption in the longer wavelength compared to azide 4.Azide 19 gave less CH insertion and more aniline products compared to azide 4 when photolyzed in toluene, suggesting that the nitro group accelerates intersystem crossing of the singlet nitrene or the singlet excited azide.Collectively, our results demonstrate that the functionalized PFPA investigated are much better in undergoing CH insertion than their nonfluorinated analogues and suggest that they may constitute an improved series of photolabeling reagents.
- Keana, John F. W.,Cai, Sui Xiong
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p. 3640 - 3647
(2007/10/02)
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