Peptidic coupling agents

Use of DCC as a Peptide Coupling Agent The final reaction needed for the Merrifield procedure is the peptide bond-forming condensation. When a mixture of an amine and an acid is treated with 7V,iV -dicyclohcxylcarbodiimidc (abbreviated DCC), the amine and the acid couple to form an amide. The molecule of water lost in this condensation converts DCC to N,N -dicyclohexyl urea (DCU). 

Connnonly used peptide coupling agents may also be used for the conversion of activated carboxylic adds into esters. Treatment of N-protected amino acids or peptides with ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxylate (EEDQ) results in mixed anhydride intermediates that produce methyl esters in the presence of excess MeOH (solvent) at room temperature. The methyl esters are conveniently isolated by aqueous acid washing of the crude residue to remove the quinoline. 

Peptide Coupling Agents, Pages 348-349, Sang-Tae Kim SummaryPlus Full Text + Links PDF (59 K)... 

There are two known methods for the formation of peptides from carbonyl and amino components. One method involves the use of adducts of phosphorus and tetrahalomethanes as coupling agents.44 The other involves the use of coupling agents such as DEPC and diphenylphosphoryl azide (DPPA)45a Both DPPA and DEPC have been shown to be effective peptide coupling agents in solution and solid-phase peptide... 

DPPA (PhO PON l as the peptide coupling agent. Thus, cyclodimerisation of the deblocked tripeptide (240), derived from (239), in the presence of DPPA and triethylamine first leads to (241) in 33% yield. Treatment of (241) with iodine in methanol next effected disulphide bridge formation to (242) which by treatment with thionyl chloride gave the natural product. In an alternative sequence to (243), the tripeptide (239) was first converted to the hexapeptide disulphide (244), using iodine in methanol, which after deprotection to (245) and double cyclisation of the latter with DPPA also gave rise to (242). 

Oxadiazoles can be prepared by acylation of amidoximes. A variation of this method gives a one-pot synthesis from the amidoxime, an organic acid and a peptide coupling agent the method is sufficiently mild that there is no racemisation when mandelic acid is used. 1,2,4-Oxadiazoles can also be prepared from amides via acylamidines, " or via the cycloaddition of nitrile oxides to nitriles, as illustrated, or to 6>-methyl oximes. ... 

Brushes with carboxylic acid or amine moieties can be used for the covalent attachment of molecules, particles, or proteins using well-established peptide coupling agents. 

Various peptide-coupling agents are commercially available as their PFg salts (4.297). The average bond lengths in the octahedral anion are P-F = 1.555 A. 

The interaction between cytochrome c and cytochrome c oxidase is mainly electrostatic in nature between lysine residues on cytochrome c and carboxyl residues on the oxidase.This allows the use of a peptide coupling agent to determine that the cytochrome c binding site on cytochrome c oxidase lies in subunit IV. Cytochrome oxidase can be resolved into two components, one of which is an electron-transport complex the other shows non-specific ion-transport properties and is buried in the enzyme, completely inaccessible to surface probes. It may be that, in cytochrome oxidase, electron transport is coupled to cation movement. 

J.K. Augustine, A. Bombrun, S. Venkatachaliah, An efficient catalytic method for the Friedlander annulation mediated by peptide coupling agent propylphosphonic anhydride (T3P) Tetrahedron. Lett. 52 (2011) 6814-6818. 

Peptide coupling agent causing little racemization. Cryst. (CCI4). Mp 94-96°. 

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