- Investigation for the cyclization efficiency of linear tetrapeptides: Synthesis of tentoxin B and dihydrotentoxin
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Investigation of the cyclization efficiency of N-methyl linear tetrapeptides using a molecular modeling study and chemical synthesis is described. The linear peptide with two N-methyl groups, MeAla-Leu-MePhe-Gly, forms γ-turn like conformation with the am
- Sato, Ryota,Oyama, Kie,Konno, Hiroyuki
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supporting information
p. 6173 - 6181
(2018/09/17)
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- Fmoc-OPhth, the reagent of Fmoc protection
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Fmoc-OSu has been widely used for Fmoc protection of amino groups, especially amino acids, in solid phase peptide synthesis. However, it has been recognized that Fmoc-βAla-OH is formed as a by-product via the Lossen rearrangement during the reaction. Since we reconfirmed the formation of Fmoc-βAla-OH during the preparation of Fmoc-AA-OH by Fmoc-OSu, Fmoc-OPhth was designed and synthesized as a new Fmoc reagent to avoid the formation of Fmoc-βAla-OH. Furthermore, Fmoc protection by Fmoc-OPhth and Fmoc-SPPS were evaluated. The various Fmoc-amino acids prepared by Fmoc-OPhth were carried out in good yields and these are applicable in Fmoc-SPPS.
- Yoshino, Ryo,Tokairin, Yoshinori,Kikuchi, Mari,Konno, Hiroyuki
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supporting information
p. 1600 - 1603
(2017/04/03)
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- A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus
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Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
- Bai, Xiaohui,Niu, Youhong,Zhu, Jingjing,Yang, An-Qi,Wu, Yan-Fen,Ye, Xin-Shan
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p. 1163 - 1170
(2016/03/01)
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- An improved synthesis of Fmoc-N-methyl-α-amino acids
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A highly efficient and environmentally more benign synthesis of Fmoc-N-methyl-α-amino acids from the corresponding Fmoc-amino acid, via intermediate 5-oxazolidinones, has been developed by using Lewis acid catalysis for the reductive opening of the oxazol
- Zhang, Suode,Govender, Thavendran,Norstroem, Thomas,Arvidsson, Per I.
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p. 6918 - 6920
(2007/10/03)
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- DNA-binding ligands from peptide libraries containing unnatural amino acids
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An unnatural peptide-based library, bound on a solid support, was screened for double-stranded-DNA (dsDNA)-binding ligands. For this purpose, fluorescein and rhodamine were used to label the single-stranded oigodeoxynucleotides. Beads containing products with affinity to dsDNA turned red in visible light and fluoresced yellow in UV light. A similar technique can be used for the selection of ligands which bind to a hairpin RNA, using a monolabelled oligoribonucleotide. The screening process revealed a high structure-affinity relationship in the successful products. Only six out of the twelve unnatural amino acids were selected, with the repeated appearance of AlaU, Sar and the secondary amino acids (Hyp, Inp). The affinity and selectivity for the target was determined using a DNase I protection assay.
- Lescrinier, Theo,Hendrix, Chris,Kerremans, Luc,Rozenski, Jef,Link, Andreas,Samyn, Bart,Van Aerschot, Arthur,Lescrinier, Eveline,Eritja, Ramon,Van Beeumen, Jozef,Herdewijn, Piet
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p. 425 - 433
(2007/10/03)
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- 'One-pot' methylation of Fmoc amino acids
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We report here a convenient method for the conversion of Fmoc amino acids to their N-methylated derivatives. The method involves reaction with formaldehyde and then reduction with triethylsilane (TES). The method is particularly attractive in that the alkylation and reduction are carried out in situ and the reaction sequence and purification of product can readily be carried out in one day. A further advantage is that the method is not restricted to α-amino acids.
- Luke, Richard W. A.,Boyce, Patrick G. T.,Dorling, E. Kate
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p. 263 - 266
(2007/10/02)
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