- 2D green SPPS: Green solvents for on-resin removal of acid sensitive protecting groups and lactamization
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Aiming at greener synthesis of complex peptides we report that conventional one-dimensional (1D) green solid-phase peptide synthesis (SPPS) is elevated to a two-dimensional (2D) concept in which side chains in peptide resins are functionalized by suitable green tactics. Specifically, we disclose on-resin deblocking using trifluoroacetic acid (TFA)/triisopropylsilane (TIS) in EtOAc/MeCN used in a synthesis of a melanocortin receptor agonist comprising (i) 1D green SPPS (ii) 2D green SPPS by an on-resin TFA/TIS in EtOAc/MeCN deprotection of Lys(Mtt) and Asp(O-2-PhiPr) followed by a lactamization using PyBOP/DIEA in NBP/EtOAc (iii) TFA cleavage followed by green precipitation using 4-methyltetrahydropyran (MTHP)/n-heptane. A further application for our green deprotection protocol was found in peptide fragment cleavages off CTC resins.
- Pawlas, Jan,Antonic, Biljana,Lundqvist, Marika,Svensson, Thomas,Finnman, Jens,Rasmussen, Jon H.
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supporting information
p. 2594 - 2600
(2019/06/13)
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- Fmoc-Amox, A Suitable Reagent for the Introduction of Fmoc
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Synthesis of most peptides is achieved using solid-phase peptide synthesis employing the Fmoc/tert-butyl strategy. However, the introduction of Fmoc in N-unprotected amino acids seems to be challenging due to the formation of dipeptides and sometimes tripeptides as impurities and β-alanyl impurities when Fmoc-OSu is used as well. Herein, we report an efficient and successful method using Fmoc-Amox, which is an oxime based derivative, toward the synthesis of Fmoc-glycine with no traces of side reactions. Fmoc-Amox is inexpensive, and Amox can be easily removed after the reaction, thus affording pure Fmoc-Gly-OH devoid of any detrimental impurities or contamination, mainly dipeptide or Amox itself, as shown by high-performance liquid chromatography and NMR, respectively.
- Kumar, Ashish,Sharma, Anamika,Haimov, Elvira,El-Faham, Ayman,De La Torre, Beatriz G.,Albericio, Fernando
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p. 1533 - 1541
(2017/10/25)
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- Penta-glycine copper(II) complexes in slightly alkaline solutions
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The kinetics of the reaction of CuII(GGG), CuII(GGGGG) and CuII(GGGGS), where G = glycine and S = sarcosine, with 4-nitrophenyl-acetate were measured. The results point out that at pH 9.0 hydroxide is an axial, or equatori
- Gaisin, Zeev,Gellerman, Gary,Meyerstein, Dan
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supporting information
p. 211 - 215
(2016/07/06)
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- Site-selective chemical cleavage of peptide bonds
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Site-selective cleavage of extremely unreactive peptide bonds is a very important chemical modification that provides invaluable information regarding protein sequence, and it acts as a modulator of protein structure and function for therapeutic applications. For controlled and selective cleavage, a daunting task, chemical reagents must selectively recognize or bind to one or more amino acid residues in the peptide chain and selectively cleave a peptide bond. Building on this principle, we have developed an approach that utilizes a chemical reagent to selectively modify the serine residue in a peptide chain and leads to the cleavage of a peptide backbone at the N-terminus of the serine residue. After cleavage, modified residues can be converted back to the original fragments. This method exhibits broad substrate scope and selectively cleaves various bioactive peptides with post-translational modifications (e.g. N-acetylation and -methylation) and mutations (d- and β-amino acids), which are a known cause of age related diseases.
- Elashal, Hader E.,Raj, Monika
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p. 6304 - 6307
(2016/05/24)
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- Hydroxymethyl Salicylaldehyde Auxiliary for a Glycine-Dependent Amide-Forming Ligation
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A new amide-forming ligation that requires a glycine or a primary amine at the linkage site is described herein. The distinguishing feature of this ligation is its reliance on an O-hydroxymethyl salicylaldehyde ester at the C-terminus which allows, via an N,O-acetal intermediate, the formation of a native peptide bond.
- Fouché, Marianne,Masse, Florence,Roth, Hans-J?rg
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supporting information
p. 4936 - 4939
(2015/11/03)
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- POLYCONJUGATES FOR DELIVERY OF RNAI TRIGGERS TO TUMOR CELLS IN VIVO
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The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand- targeted amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or conjugate) are further covalently linked to an RNAi trigger.
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Page/Page column 37
(2015/02/25)
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- Benzotriazole reagents for the syntheses of Fmoc-, Boc-, and Alloc-protected amino acids
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Stable Fmoc-, Boc-, and Alloc-benzotriazoles react with various amino acids including unprotected serine and glutamic acid, in the presence of triethylamine at 20° as reagents to introduce -amino protecting groups to afford Fmoc-, Boc-, and Alloc-protected amino acids (77-94%) free of dipeptide and tripeptide impurities. Fmoc-, and Alloc-Gly-Gly-OH dipeptides were prepared in 90% yields by N-acylation of glycylglycine with Fmoc- and Alloc-benzotriazoles in the presence of triethylamine. Synthesized N-protected amino acids were greater than 99% pure, analyzed by HPLC. Georg Thieme Verlag Stuttgart - New York.
- Ibrahim, Tarek S.,Tala, Srinivasa R.,El-Feky, Said A.,Abdel-Samii, Zakaria K.,Katritzky, Alan R.
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p. 2013 - 2016
(2011/10/08)
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- Oxime carbonates: Novel reagents for the introduction of fmoc and alloc protecting groups, free of side reactions
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Fmoc and Alloc protecting groups represent a consistent alternative to classical Boc protection in peptide chemistry. The former was established in the last decades as the α-amino protecting group of choice, whereas the latter allows a fully orthogonal protection strategy with Fmoc and Boc. Usually, the introduction of the Fmoc and Alloc moieties takes place through their halogenoformates, azides, or activated carbonates. This rather simple reaction is accompanied by several side reactions, specially the formation of Fmoc/Alloc dipeptides and even tripeptides. The present work describes new promising Fmoc/Alloc-oxime reagents, which are easy to prepare, stable, and highly reactive crystalline materials that afford almost: contaminant-free Fmoc/Alloc-amino acids in high yields by following a conventional procedure. Amongst the Fmoc-oxime derivatives, the N-hydroxypicolimmidoyl cyanide derivative (N-([(9H-fluoren-9-yl)methoxy]carbonyloxy}picolinimidoyl cyanide) gave the best results for the preparation of Fmoc-Gly-OH, which is the most predisposed to give side reactions. The same Alloc-oxime analogue afforded the preparation of Alloc-Gly-OH in good yield, purity, and extremely low dipeptide formation, as analyzed by reverse-phase HPLC and NMR spectroscopy.
- Khattab, Sherine N.,Subiros-Funosas, Ramon,El-Faham, Ayman,Albericio, Fernando
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experimental part
p. 3275 - 3280
(2010/09/05)
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- Supramolecular Hydrogels Respond to Ligand-Receptor Interaction
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N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions. These hydrogels respond to a ligand?receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition. Copyright
- Zhang, Yan,Gu, Hongwei,Yang, Zhimou,Xu, Bing
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p. 13680 - 13681
(2007/10/03)
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- Synthesis and application of a novel, crystalline phosphoramidite monomer with thiol terminus, suitable for the synthesis of DNA conjugates
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A new, crystalline 5′-thiol modifier phosphoramidite monomer (3), suitable for DNA synthesis, has been prepared. This monomer has been built into an oligonucleotide using the standard protocol. After cleavage, purification and removal of the trityl group
- Kupihar, Zoltan,Schmel, Zoltan,Kele, Zoltan,Penke, Botond,Kovacs, Lajos
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p. 1241 - 1247
(2007/10/03)
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