846549-33-5Relevant academic research and scientific papers
Site-specific protein immobilization by Staudinger ligation
Soellner, Matthew B.,Dickson, Kimberly A.,Nilsson, Bradley L.,Raines, Ronald T.
, p. 11790 - 11791 (2003)
The Staudinger ligation between an azido-protein and a phosphinothioester-derivatized surface is demonstrated to be an effective means for the site-specific, covalent immobilization of a protein. Immobilization yields of >50% are obtained in 80% of their expected activity. No other method enables more rapid immobilization or a higher yield of active protein. Because azido-peptides and azido-proteins are readily attainable by synthesis, biosynthesis, or semisynthesis, the Staudinger ligation could be of unsurpassed utility in creating microarrays of functional peptides and proteins. Copyright
An in situ combinatorial methodology to synthesize and screen chemical probes
Van Der Zouwen, Antonie J.,Lohse, Jonas,Wieske, Lianne H. E.,Hohmann, Katharina F.,Van Der Vlag, Ramon,Witte, Martin D.
supporting information, p. 2050 - 2053 (2019/02/19)
Chemical probes that label proteins of interest in the context of complex biological samples are useful research tools. The reactive group that forms the covalent bond with the target protein has a large effect on the selectivity and selecting the appropriate group determines the success of a probe. We here report the development of a combinatorial methodology based on imine chemistry that enables straightforward in situ synthesis and screening of different reactive groups and thereby simplifies identification of probe leads. Using our methodology, we found chemical probes targeting BirA and chloramphenicol acetyl transferase, two proteins associated with antibacterial activity and resistance.
A Versatile Approach for Site-Specific Lysine Acylation in Proteins
Wang, Zhipeng A.,Kurra, Yadagiri,Wang, Xin,Zeng, Yu,Lee, Yan-Jiun,Sharma, Vangmayee,Lin, Hening,Dai, Susie Y.,Liu, Wenshe R.
supporting information, p. 1643 - 1647 (2017/02/05)
Using amber suppression in coordination with a mutant pyrrolysyl-tRNA synthetase-tRNAPylpair, azidonorleucine is genetically encoded in E. coli. Its genetic incorporation followed by traceless Staudinger ligation with a phosphinothioester allows the convenient synthesis of a protein with a site-specifically installed lysine acylation. By simply changing the phosphinothioester identity, any lysine acylation type could be introduced. Using this approach, we demonstrated that both lysine acetylation and lysine succinylation can be installed selectively in ubiquitin and synthesized histone H3 with succinylation at its K4 position (H3K4su). Using an H3K4su-H4 tetramer as a substrate, we further confirmed that Sirt5 is an active histone desuccinylase. Lysine succinylation is a recently identified post-translational modification. The reported technique makes it possible to explicate regulatory functions of this modification in proteins.
Chemoselective Nitrile Oxide-Alkyne 1,3-Dipolar Cycloaddition Reactions from Nitroalkane-Tethered Peptides
Reja, Rahi M.,Sunny, Sereena,Gopi, Hosahudya N.
supporting information, p. 3572 - 3575 (2017/07/17)
Synthesis and incorporation of a new amino acid with a nitroalkane side chain into peptides, in situ transformation of a nitroalkane side chain into nitrile oxide, and chemoselective 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxide and different alkynes are reported. The nitroalkane-mediated nitrile oxide-alkyne cycloaddition was found to be orthogonal to the copper(I)-catalyzed azide-alkyne cycloaddition reaction. The combination of orthogonal nitrile oxide-alkyne and azide-alkyne cycloaddition reactions can be explored to tailor different 1,2,3-triazole and 3,5-isoxazoles, respectively, on the peptide backbone.
Native chemical ubiquitination using a genetically incorporated azidonorleucine
Yang, Renliang,Bi, Xiaobao,Li, Fupeng,Cao, Yuan,Liu, Chuan-Fa
supporting information, p. 7971 - 7974 (2014/07/08)
A robust chemical ubiquitination method was developed. The method employed a genetically incorporated azidonorleucine as an orthogonal lysine precursor for the installation of a Gly residue bearing an Nα-auxiliary which mediated the ligation between ubiquitin(1-75)-thioester and the target protein. To demonstrate our methodology, a model protein, K48-linked diubiquitin, was synthesized with an overall yield of 35%. the Partner Organisations 2014.
Clickable Cγ-azido(methylene/butylene) peptide nucleic acids and their clicked fluorescent derivatives: Synthesis, DNA hybridization properties, and cell penetration studies
Jain, Deepak R.,Ganesh, Krishna N.
, p. 6708 - 6714 (2014/08/05)
Synthesis, characterization, and DNA complementation studies of clickable Cγ-substituted methylene (azm)/butylene (azb) azido PNAs show that these analogues enhance the stability of the derived PNA:DNA duplexes. The fluorescent PNA oligomers synthesized by their click reaction with propyne carboxyfluorescein are seen to accumulate around the nuclear membrane in 3T3 cells.
17α-ethynylestradiol peptide labeling by 'click' chemistry
Bol'Shakov, Oleg I.,Lebedyeva, Iryna O.,Katritzky, Alan R.
, p. 2926 - 2932 (2012/10/29)
A synthesis of 17α-ethynylestradiol-labeled native peptides is reported. The peptide moiety is tethered to the steroid hormone by a 1,2,3-triazole bridge formed by a CuAAC reaction in which the azido group of the peptide combines with the terminal acetylenic moiety of ethynylestradiol to link the two bioactive molecules. Thus bioconjugates containing the hormone moiety at three positions within the peptide molecule could be useful targets for hormono-enzyme interaction studies. Georg Thieme Verlag Stuttgart ? New York.
New β-strand templates constrained by Huisgen cycloaddition
Pehere, Ashok D.,Abell, Andrew D.
supporting information; experimental part, p. 1330 - 1333 (2012/05/20)
New peptidic templates constrained into a β-strand geometry by linking acetylene and azide containing P1 and P3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a β-strand are shown to be potent inhibitors of the protease calpain. The β-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.
Solid-phase total synthesis of (-)-apratoxin a and its analogues and their biological evaluation
Doi, Takayuki,Numajiri, Yoshitaka,Takahashi, Takashi,Takagi, Motoki,Shin-Ya, Kazuo
supporting information; experimental part, p. 180 - 188 (2011/10/08)
Two approaches for the solid-phase total synthesis of apratoxinA and its derivatives were accomplished. In synthetic route A, the peptide was prepared by the sequential coupling of the corresponding amino acids on trityl chloride SynPhase Lanterns. After cleavage from the polymer-support, macrolactamization of 10, followed by thiazoline formation, provided apratoxinA. This approach, however, resulted in low yield because the chemoselectivity was not sufficient for the formation of the thiazoline ring though its analogue 33 was obtained. However, in synthetic route B, a cyclization precursor was prepared by solid-phase peptide synthesis by using amino acids 13-15 and 18. The final macrolactamization was performed in solution to provide apratoxin A in high overall yield. This method was then successfully applied to the synthesis of apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then evaluated. The epimer 34 was as potent as apratoxinA, and O-methyl tyrosine can be replaced by 7-azidoheptyl tyrosine without loss of activity. The 1,3-dipolar cycloaddition of 38 with phenylacetylene was performed in the presence of a copper catalyst without affecting the thiazoline ring. Solid Approach: Two routes for the solid-phase total synthesis of apratoxinA have been described. On the basis of this method, its analogues were synthesized and their biological activity has been evaluated. Copyright
Orthogonal alkynyl amino acid reporter for selective labeling of bacterial proteomes during infection
Grammel, Markus,Zhang, Mingzi M.,Hang, Howard C.
supporting information; experimental part, p. 5970 - 5974 (2010/11/05)
(figure Presented) Bacterial proteins in the haystack: The alkynyl amino acid reporter AOA (see scheme) can be used to visualize and identify newly synthesized bacterial proteins during Salmonella infection of mammalian cells by the copper(I)-catalyzed az
