Peptides coupling, 1 -ethyl-3- carbodiimide

Williams, A., and Ibrahim, I. A. (1981) A mechanism involving cyclic tautomers for the reaction with nucleophiles of the water-soluble peptide coupling reagent l-ethyl-3-(3-dimethyla-minopropyl) carbodiimide (EDC). J. Am. Chem. Soc. 103, 7090—7095. 

The MAf -dicyclohexylurea that is produced in peptide couplings with DCCI is soluble in the same solvents as the product, making it more difficult to separate the by-products during purification. An alternative carbodiimide used in peptide synthesis is l-ethyl-3-(3-dimethylaminopropyl) carbodiimide, known as EDCI. Both EDCl and the urea that is produced from it are water-soluble and can be more easily separated from the peptide product. EDCI can also be used in organic solvents. 

Figure 1 Conjugation reactions for coupling peptides to the surface of preformed liposomes. Functionalized lipophilic anchors were incorporated into liposomes and reacted with the peptides in aqueous media. Reactive endgroup functions (A) maleimide (B) bromo- or iodoacetyl (C) 2-pyridyldithio (D) carboxylic acid (E) />-nitrophenyl carbonate and (F) hydrazide. Abbreviations EDC, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide NHS, 7V-hydroxysuccinimide.

Carbodiimide Coupling of Peptides to Carrier Proteins with 1 -Ethyl-3-(3-Dimethylaminopropyl)-Carbodiimide (EDAC, EDO... 

Monomer synthesis from 3-(4 -hydroxyphenyl) propionic acid and tyrosine alkyl esters w as accomplished by carbodiimide mediated coupling reactions, following known procedures of peptide synthesis (Pulapura, 1992 Ertel, 1994) in typical yields of 70%. Monomers carrying an ethyl, butyl, hexyl, or octyl ester pendent chain were investigated extensively (Ertel, 1994 Hooper, 1995). These peptide-like diphenolic monomers were used as starting materials in the synthesis of polycarbonates, polyiminocarbonates, and polyarylates. 

Figure 17.3. Methods for conjugating Qdots to biomolecules, (a) Traditional covalent cross-linking chemistry using EDAC (ethyl-3-dimethyl amino propyl carbodiimide) as a catalyst, (b) Conjugation of antibody fragments to Qdots via reduced sulfhydry 1-amine coupling. SMCC, succinimidyl-4-N-maleimidomethyl-cyclohexane carboxylate. (c) Conjugation of antibodies to Qdots via an adaptor protein, (d) Conjugation of histidine-tagged peptides and proteins to Ni-NTA-modified Qdots, with potential control of the attachment site and Qdotrligand molar ratios. [Reproduced with permission from Elsevier.)...

Another potential problem with DCC is that at the completion of the reaction some DCU remains in solution with the product, necessitating additional purification. Water-soluble carbodiimide derivatives such as l-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide Metho-p-toluenesulffonate and l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide Hydrochloride (EDCI) obviate this problem, as they are removed by a simple extraction. Many newer coupling agents have been developed for peptide synthesis and other acylation reactions. These include Benzotriazol-l-yloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)," 0-Benzotriazol-l-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU)," Bis(2-oxo-3-oxazolidinyl)phosphinic Chloride (BOP-Cl), and (1 //-1,2,3-benzotriazol-1 -yloxy)tris(pyrTolidino)phosphonium hexafluorophosphate (PyBOP). In addition to linear and polymeric amides, lactams of various ring sizes have been synthesized using these methods (eq 1)."... 

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