- Synthesis of lucifensin by native chemical ligation and characteristics of its isomer having different disulfide bridge pattern
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The antimicrobial 40-amino-acid-peptide lucifensin was synthesized by native chemical ligation (NCL) using N-acylbenzimidazolinone (Nbz) as a linker group. NCL is a method in which a peptide bond between two discreet peptide chains is created. This method has been applied to the synthesis of long peptides and proteins when solid-phase synthesis is imcompatible. Two models of ligation were developed: [15 + 25] Ala-Cys and [19 + 21] His-Cys. The [19 + 21] His-Cys method gives lower yield because of the lower stability of 18-peptide-His-Nbz-CONH2 peptide, as suggested by density functional theory calculation. Acetamidomethyl-deprotection and subsequent oxidation of the ligated linear lucifensin gave a mixture of lucifensin isomers, which differed in the location of their disulfide bridges only. The dominant isomer showed unnatural pairing of cysteines [C1-6], [C3-5], and [C2-4], which limits its ability to form α-helical structure. The activity of isomeric lucifensin toward Bacillus subtilis, Staphylococcus aureus, and Micrococcus luteus was lower than that of the natural lucifensin. The desired product native lucifensin was prepared from this isomer using a one-pot reduction with dithiotreitol and subsequent air oxidation in slightly alkaline medium. Copyright
- Stanchev, Stancho,Zawada, Zbigniew,Monincová, Lenka,Bednárová, Lucie,Slaninová, Ji?ina,Fu?ík, Vladimír,?e?ovsky, Václav
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- Benzimidazolinone-Free Peptide o-Aminoanilides for Chemical Protein Synthesis
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The thioester surrogate 3,4-diaminobenzoic acid (Dbz) facilitates the efficient synthesis of peptide thioesters by Fmoc chemistry solid phase peptide synthesis and the optional attachment of a solubility tag at the C-terminus. The protection of the partially deactivated ortho-amine of Dbz is necessary to obtain contamination-free peptide synthesis. The reported carbamate protecting groups promote a serious side reaction, benzimidazolinone formation. Herein we introduce the Boc-protected Dbz that prevents the benzimidazolinone formation, leading to clean peptide o-aminoanilides suitable for the total chemical synthesis of proteins.
- Mannuthodikayil, Jamsad,Singh, Sameer,Biswas, Anamika,Kar, Abhisek,Tabassum, Wahida,Vydyam, Pratap,Bhattacharyya, Mrinal Kanti,Mandal, Kalyaneswar
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- Head-to-tail macrocyclization of cysteine-free peptides using an o-aminoanilide linker
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A head-to-tail macrocyclization protocol for the preparation of cysteine-free cyclic peptides was investigated. The o-aminoanilide linker constructed in the peptide sequence by a standard Fmoc-based peptide synthesis procedure was subjected to nitrite-med
- Ohara, Takumi,Kaneda, Masato,Saito, Tomo,Fujii, Nobutaka,Ohno, Hiroaki,Oishi, Shinya
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- Peptide o-aminoanilides as crypto-thioesters for protein chemical synthesis
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Fully unprotected peptide o-aminoanilides can be efficiently activated by NaNO2 in aqueous solution to furnish peptide thioesters for use in native chemical ligation. This finding enables the convergent synthesis of proteins from readily synthesizable peptide o-aminoanilides as a new type of crypto-thioesters. The practicality of this approach is shown by the synthesis of histone H2B from five peptide segments. Purification or solubilization tags, which are sometimes needed to improve the efficiency of protein chemical synthesis, can be incorporated into the o-aminoanilide moiety, as demonstrated in the preparation of the cyclic protein lactocyclicin Q.
- Wang, Jia-Xing,Fang, Ge-Min,He, Yao,Qu, Da-Liang,Yu, Min,Hong, Zhang-Yong,Liu, Lei
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- GLUCOSE SENSITIVE INSULINS AND USES THEREOF
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The present invention provides glucose sensitive insulin derivatives comprising a macrocycle, a glucose mimetic and human insulin or an analogue thereof, and their pharmaceutical use. Furthermore, the invention relates to pharmaceutical compositions compr
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Page/Page column 31
(2020/04/25)
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- MACROCYCLIC COMPOUNDS
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The present invention relates to macrocyclic compounds which are capable of selective binding to a target saccharide (e.g. glucose), making them particularly well suited for use in saccharide sensing applications. The present invention also relates to processes for the preparation of said compounds, to compositions and devices comprising them, and to their use in the detection of a target saccharide.
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Paragraph 00238
(2018/10/19)
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- Hybrid phase ligation for efficient synthesis of histone proteins
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We introduce a hybrid solid-solution phase ligation approach that combines the efficiency of solid phase ligation with solution phase ligation in the total synthesis of modified histone proteins. A two linker strategy allows analysis throughout work on the solid phase and maximizes yields through cleavage at an external Rink, while an internal HMBA linker allows the native carboxyl terminus for any protein sequence. We demonstrate this approach for two histone proteins: Triple-acetylated H4-K5ac, K12ac, K91ac and CENP-A-K124ac.
- Yu, Ruixuan R.,Mahto, Santosh K.,Justus, Kurt,Alexander, Mallory M.,Howard, Cecil J.,Ottesen, Jennifer J.
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supporting information
p. 2603 - 2607
(2016/03/05)
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- One-pot total chemical synthesis of human α-synuclein
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Post-translational modifications (PTMs) regulate key aspects of the physiological and pathogenic properties of Parkinson's disease-associated presynaptic protein α-synuclein. We herein describe a one-pot total chemical synthesis that should enable site-specific introduction of single or multiple PTMs or small molecule probes essentially at any site within the protein.
- Fauvet, Bruno,Butterfield, Sara M.,Fuks, Jonas,Brik, Ashraf,Lashuel, Hilal A.
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supporting information
p. 9254 - 9256
(2013/10/01)
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- An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation
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(Chemical Equation Presented) Intramolecular activation of C-terminal peptides: Mildly activated N-acylurea peptides are readily formed on the solid support following chain assembly, avoiding over-activation of the C-terminus. The utility of these peptide
- Blanco-Canosa, Juan B.,Dawson, Philip E.
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supporting information; experimental part
p. 6851 - 6855
(2009/04/07)
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