Peptides, copper chloride

The infrared spectra of glycylglycine mixed with copper chloride in a 1 1 molar ratio in D2O solution (total concentration of the ligand and the metal is 0.2333M) (Kim and Martell, 1964) are shown in Fig. 9.2. As shown above, glycylglycine displays three bands at 1720, 1675, and 1595 cm at pD 3.58. However, at the same pD value, the mixture displays one extra band at 1625 cm This band was attributed to the peptide carbonyl of the metal complex (L) which was formed by the... 

Te-Velde G, Baerends EJ (1992) Nrrmerical integration for polyatomic systems. J Comput Phys 99 84-98 Te-Velde G (1995) Amsterdam Density Fimctional 2.0.1, Users Guide, Vtije Universiteit, Amsterdam Texler NR, Rode BM (1997) Monte Carlo simirlations of copper chloride solutions at various concentrations including full 3-body correction terms. Chem Phys 222 281-288 Texler NR, Holdway S, Neilson GW, Rode BM (1998) Monte Carlo simulations and neutron diffraction studies of the peptide forming system 0.5 mol kg CuCl2-5 mol kg NaCl-H20 at 293 and 353 K. J Chem Soc Faraday T 94 59-65... 

Carbodiimide peptide synthesis. 1 -Hydroxybenzotriazole (HOBt) is frequently used to suppress racemization in peptide syntheses using carbodiimides. Copper(II) chloride decreases racemization, but also depresses the yield markedly. By judicious use of both additives, racemization can be prevented with only slight effect on the yield. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

T Miyazawa, T Otomatsu, Y Fukui, T Yamada, S Kuwata. Racemization-free and efficient peptide synthesis by the carbodiimide method using 1-hydroxybenzotriazole and copper(II) chloride simultaneously as additives. J Chem Soc Chem Commun 419, 1988. 

T Miyazawa, T Donkai, T Yamada, S Kuwata. Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the mixed-anhydride and related methods. Int J Pept Prot Res 40, 49, 1992. 

Afterward, the peptide chain was elongated following the standard Fmoc-based protocol. Before cleavage of the peptide the incorporated Mmt-protected cysteine was deprotected using 1% TFA. Under these very mild conditions the farnesyl moiety was not harmed. Palmitoylation could he achieved using an excess of palmitoyl chloride. Cleavage with copper acetate and methanol as a nucleophile gave the farnesylated and palmitoylated N-Ras sequence with the C-terminal methyl ester 78. ... 

These problems were solved by Miller,[104 who developed a direct isourea-mediated 3-elimination process to prepare DHA derivatives. The reaction involves treatment of a Ser (or Thr) peptide 30 with a carbodiimide (1.1 equivalents) in the presence of copper(I) chloride as a catalyst to give a AAla (or AAbu) derivative 31, respectively, in good yield (Scheme 11). 

Dimethyl N(p-tosyl)sulfoximine. pentafulvalenes Copper(II) chloride. peptides 0-Benzotriazolyl-N,N,N, N -tetra-methyluronium hexafluorophosphate. l-(3-Dimethylaminopropyl)-3-ethylcarbodi-imide. Di(N-succinimidyl)oxalate. Tetra-... 

In the laboratory of R. Bihovsky, a series of peptide mimetic aldehyde inhibitors of calpain I was prepared in which the P2 and P3 amino acids were replaced with substituted 3,4-dihydro-1,2-benzothiazine-3-carboxylate-1,1-dioxides. The synthesis began with the diazotization of the substituted aniline substrate using sodium nitrite and hydrochloric acid. The aqueous solution of the corresponding diazonium chloride product was added dropwise to the solution of acrylonitrile in a water-acetone mixture, which contained catalytic amounts of copper(ll) chloride. This Meerwein arylation step afforded the chloronitrile derivative, which was subjected to sulfonation with chlorosulfonic acid, and the resulting sulfonyl chloride was treated with the solution of ammonia in dioxane to give the desired 3,4-dihydro-1,2-benzothiazine-2-carboxamide. 

The first step in this new stain protocol employs copper acetate, a metal salt that is both a good fixative ( ) and a silver stain enhancer. The mechanism of copper s stain enhancement, in this and other silver stains, may be similar to its action in the biuret reaction (15.), in which a characteristic color shift, from violet to pink, is achieved by titrating peptides in the presence of copper ions. Copper complexes formed with the N-peptide atoms of the peptide bonds are primarily responsible for this reaction. There are also some number of secondary sites which may interact with copper. Any elemental copper formed may displace positive silver ions from solution as copper has a greater tendency to donate electrons than silver, indicated by its position in the electromotive series of the elements. Following the treatment with copper acetate, the membrane is sequentially soaked in a solution containing chloride and citrate ions and then in a solution containing silver nitrate. The membrane is then irradiated with light while it is in the silver nitrate... 

It has been known for some time that ligands 27, 35, and 36 can be used for direct synthesis of oxidized Cu(I) chloride solutions which are useful catalysts for oxidative coupling processes (26,27). Amide and lactam ligands contain the nitrogen atoms of amines (which generally promote Cu(I) oxidation, see above) and also serve as crude models for the peptide link of proteins, which is the general environment of copper found in oxidases (28). 

In quite different new approaches to peptide bond synthesis treatment of Gly-OEt with copper(II) chloride in ethanol was found to yield di-, tri-, and tetra-Gly-OEt derivatives, and a four-component condensation approach with computer planning has been summarized. ... 

Racemization Suppression in Peptide Couplings. A mixture of copper(It) chloride and triethylamine catalyzes the formation of peptide bonds. Furthermore, when used as an additive, CuCl2 suppresses racemization in both the carbodiimide and mixed anhydride peptide coupling methods. Recently it was shown that a combination of 1-hydroxybenzotriazole and CuCl2 gives improved yields of peptides while eliminating racemization. ... 

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