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Solid phase synthesis of a tetrapeptide labelled with Carbon‐13. Preparation of L‐[U‐ 13 C]lysyl‐L‐[1‐ 13 C]arginyl‐L‐[3‐ 13 C]asparyl‐L‐[1‐ 13 C]serine
Author(s) -
Humbert Thierry,
Marsura Alain,
LuuDuc Cuong
Publication year - 1992
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580310304
Subject(s) - chemistry , tetrapeptide , peptide synthesis , trifluoroacetic acid , carbodiimide , solid phase synthesis , ninhydrin , protecting group , stereochemistry , methylene , thermolysin , amino acid , peptide , medicinal chemistry , organic chemistry , biochemistry , alkyl , trypsin , enzyme
Synthesis of a [ 13 C] tetrapeptide L‐[U‐ 13 C]Lysyl‐L‐[1‐ 13 C]Arginyl‐L‐[3‐ 13 C]Aspartyl‐L‐[1‐ 13 C] Serine (KRDS) on a p ‐alkoxybenzyl ester polystyrene‐1% divinylbenzene resin support is described by using repetitive nonhydrolytic base cleavage of α‐amino protective groups in Solid Phase Peptide Synthesis (SPPS). Protected [ 13 C] amino acid (AA) used in this SPPS model were prepared with 9‐Fluorenylmethyloxycarbonyl (Fmoc) protecting group and with different acid labile side chain protecting group over AA type as: Fmoc‐Ser( tert ‐Bu)‐OH, Fmoc‐Asp( tert ‐Bu)‐OH, Fmoc‐Arg(Pmc)‐OH and Fmoc‐Lys(Fmoc)‐OH. All the protected AA were coupled by N,N′ ‐dicyclohexyl carbodiimide (DCC) procedure, followed by Fmoc group cleavage using 20% piperidine in N,N dimethylacetamide (DMA). Quantitative deblocking side‐chain AA protection and removal of KRDS from the solid support was effected by treatment with 50% trifluoroacetic acid in methylene chloride in a one pot‐procedure. Homogeneous free [ 13 C] KRDS was obtained in 90% overall yield after HPLC purification. This synthesis schedule offered the advantage over present solid phase method which used acidolysis for repetitive α‐amino group deblocking.