Home Peptide SynthesisResins for the Fmoc-/tBu-Synthesis of Peptide Acids

Resins for the Fmoc-/tBu-Synthesis of Peptide Acids

The TFA-labile Wang resin is a standard support for batch synthesis of peptide acids following the Fmoc-/tBu-protection scheme.^(1,2) It is easily cleaved by treatment with 95% TFA. Special attention should be given to the attachment of the first amino acid residue to this benzyl alcohol type support, because the activation step can lead to a substantial degree of racemization. For the incorporation of the C-terminal amino acids, the following coupling methods are recommended: carbodiimide/dimethyl aminopyridine (DMAP) in dichloromethane,⁽³⁾ 2,6-dichlorobenzoyl chloride/pyridine in dimethyl formamide (DMF),⁽⁴⁾ 1- hydroxybenzotriazole (HOBt)/N,N´-dicyclohexylcarbodiimide (DCC) in DMF (catalytic amounts of DMAP optional),⁽⁵⁾ 1-(2- mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole (MSNT) in the presence of N-methylimidazole,⁽⁶⁾ or the Mitsunobu coupling reaction.^(7,8)

Materials

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References

1.

Wang S. 1973. p-Alkoxybenzyl Alcohol Resin andp-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments. J. Am. Chem. Soc.. 95(4):1328-1333. https://doi.org/10.1021/ja00785a602

2.

Fields CG, Fields GB. Solvents for Solid-Phase Peptide Synthesis.29-40. https://doi.org/10.1385/0-89603-273-6:29

3.

Chang C, Meienhofer J. SOLID-PHASE PEPTIDE SYNTHESIS USING MILD BASE CLEAVAGE OF N?FLUORENYLMETHYLOXYCARBONYLAMINO ACIDS, EXEMPLIFIED BY A SYNTHESIS OF DIHYDROSOMATOSTATIN. 11(3):246-249. https://doi.org/10.1111/j.1399-3011.1978.tb02845.x

4.

Sieber P. 1987. An improved method for anchoring of 9-fluorenylmethoxycarbonyl-amino acids to 4-alkoxybenzyl alcohol resins.. Tetrahedron Letters. 28(49):6147-6150. https://doi.org/10.1016/s0040-4039(00)61832-4

5.

GRANDAS A, JORBA X, GIRALT E, PEDROSO E. Anchoring of Fmoc-amino acids to hydroxymethyl resins. 33(5):386-390. https://doi.org/10.1111/j.1399-3011.1989.tb00699.x

6.

Blankemeyer-Menge B, Nimtz M, Frank R. 1990. An efficient method for anchoring fmoc-anino acids to hydroxyl-functionalised solid supports. Tetrahedron Letters. 31(12):1701-1704. https://doi.org/10.1016/s0040-4039(00)88858-9

7.

Mitsunobu O. 1981. Synthesis . 1.

8.

Krch?ák V, Cabel D, Weichsel A, Flegelová Z. 1995. Esterification of polymer-supported hydroxyl groups using the Mitsunobu reaction. Lett Pept Sci. 1(6):277-282. https://doi.org/10.1007/bf00119768