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Potential pyrophosphate formation upon use of N α-Fmoc-Tyr(PO3H2)-OH in solid-phase peptide synthesis

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Summary

A series of peptides related to some of the autophosphorylation sites of the epidermal growth factor receptor has been synthesized on solid phase, using side-chain-unprotected phosphotyrosine. Although the desired peptides could be obtained, this approach was not entirely satisfactory due to a side reaction that gave the pyrophosphate derivative of the target peptide. Under identical coupling conditions, the extension of this side reaction appears to be sequence dependent.

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Abbreviations

BOP:

benzotriazolyloxy-tris-(dimethylamino)phosphonium hexafluorophosphate

DCM:

dichloromethane

DIEA:

diisopropylethylamine

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

FABMS:

fast atom bombardment mass spectrometry

Fmoc:

fluorenylmethoxycarbonyl

HATU:

N-[(dimethylamino)1H-1,2,3-triazolo[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide

HOBt:

1-hydroxybenzotriazole

HPLC:

high-performance liquid chromatography

MALDI-TOF:

matrix-assisted laser-desorption ionization time-of-flight mass spectrometry

MBHA:

4-methylbenzhydrylamine resin

PAL:

tris(alkoxy)benzylamide linker

PEG:

polyethylene glycol

TFA:

trifluoroacetic acid

TPTU:

2-(2-pyridon-1-yl)-1,1,3,3-tetramethyluroniumfluoroborate

tR :

retention time

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Authors and Affiliations

  1. Pharmaceuticals Division, Ciba-Geigy Ltd., CH-4002, Basel, Switzerland

    Carlos García-Echeverría

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  1. Carlos García-Echeverría
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Abbreviations used for amino acids follow the recommendations of the IUPAC-IUB Commission of Biochemical Nomenclature [Eur. J. Biochem., 138 (1984) 9].

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García-Echeverría, C. Potential pyrophosphate formation upon use of N α-Fmoc-Tyr(PO3H2)-OH in solid-phase peptide synthesis. Lett Pept Sci 2, 93–98 (1995). https://doi.org/10.1007/BF00128503

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  • DOI: https://doi.org/10.1007/BF00128503

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