Imidazole peptide coupling

Carbonyldiimidazole does certainly stand out as one of the most remarkable reagents for peptide coupling. Carboxylic acids react readily with this reagent to yield acyl imidazoles which in turn couple with the amino group of a peptide to produce a new acyl-nitrogen linkage with very little racemization. Reaction of the acylimidazolide with other nucleophiles can lead to a variety of carbonyl derivatives (62AG(E)35l). 

Note, however, that Beyerman, Weygand, et al. observed that imidazole caused racemization in a number of peptide couplings and is less effective than 1,2,4-triazole. 

Mono and 6iftrialkyisilyl derivatives of amines are hydrolyzed by water, so that they have limited value as protecting groups. Riihlmann and Kuhrt [266] have prepared amino acid esters by the alkylation of 6iytrimethylsilylglycine esters (44) and A-trimethylsilyl peptide trimethylsilyl esters have been employed in imidazole-activated peptide coupling [267]. The... 

Protection of —SH Groups.—Although silylation of functional groups has become a valuable means of transient protection, and can be applied to thiols (RSH -> RSSiMea using hexamethyldisilazane and imidazole), " S-protection problems are mostly those of cysteine, and must be solved so that peptide-coupling and selective de-protection techniques can be applied. The S-acetamidomethyl group " has been put to use in protection of the... 

Nickel(III) peptide complexes have a tetragonally-distorted octahedral geometry as shown by electron spin resonance studies (19) and by reaction entropies for the Ni(III,II) redox couple (17). Axial substitutions for Ni(III)-peptide complexes are very fast with formation rate constants for imidazole greater... 

Related to such transacylations is the ability of triazole to accept and transfer acyl groups so as to make it a catalyst for the formation of amides and esters from their constituents. In particular triazole has been used in the synthesis of peptides. Imidazole and 1,2,3-triazole which also possess both weakly acidic and weakly basic groups have similar catalytic action which, however, is accompanied by racemization not observed when 1,2,4-triazole was used (65RTC213). It has been found best to catalyze coupling in peptide syntheses such as Scheme 144 (66LA(69l)2l2). For the use of quinolinesulfonyl-3-nitrotriazolide in nucleotide synthesis see (80TL4339). 

Two-dimensional PISEMA spectra experimentally obtained from powder samples are analyzed by comparison with simulations to determine Euler angles that define the orientation of the CSA tensor in the molecular frame, while the magnitudes of the CSA tensor is measured from a ID chemical shift powder pattern. Some examples of PISEMA spectra of powder samples simulated using SIMPSON program 5 are shown in Fig. 6. PISEMA spectra correlating the N chemical shift and the ll 5r dipolar coupling interactions associated with an amide site of a peptide (Fig. 6(A)) and with the N -H bond of the imidazole ring in histidine (Fig. 6(B)) were simulated. 

This peptide was modified with two redox-active groups, a Ru (bpy)2 imidazole at one free histidine, and a Ru(NH3)4(pyridine) at the remaining free histidine (bpy is 2,2 -bipyridine). To avoid frayed ends of the peptide, the histidines are placed at least 6 residues from either terminus. CD spectroscopy confirmed that the addition of these inorganic groups did not perturb the hehcal structure of the peptide. It will be of interest to compare ET rates from this system with rates in helical bundles to assess whether the presence of interhelix interactions in the de novo metalloprotein exerts an influence on the electronic coupling of donor and acceptor. 

An early example of this approach was that of Lautsch et al. who coupled various histidine-containing tripeptides to the propionic acid side-chains of mesoporphyrin IX la (Scheme 2). After metal insertion into the porphyrin, intramolecular coordination by the histidyl imidazole was possible depending on the length of the peptide chain. Similarly, histidine-containing peptides were attached to the ethyl side chains of mesoporphyrin IX via sulfide linkages to give 2(b-d), a situation similar to that in cytochrome c. Losse and Miiller coupled L-histidine methylester and protohemin 3 with dicyclohexylcar-... 

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