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Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast
Author(s) -
Thim Lars,
Norris Kjeld,
Norris Fanny,
Nielsen Per F.,
Bjørn Søren E.,
Christensen Mogens,
Petersen Jørgen
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80543-4
Subject(s) - trefoil , yeast , peptide , biochemistry , chemistry , biology , agronomy
Recombinant human spasmolytic polypeptide (r‐hSP) has been produced in relatively large amounts in Saccharomyces cerevisiae . The two intronless trefoil domains of the hSP‐DNA were cloned separately by PCR from human genomic DNA, and the remaining parts of the gene synthezised. Recombinant plasmids were constructed to encode a fusion protein consisting of a hybrid leader sequence and the hSP sequence. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Kex 2 processing enzyme system. The secreted r‐hSP was found in a glycosylated and an non‐glycosylated form. The two forms of r‐hSP were purified from the yeast fermentation broth by a combination of ion‐exchange chromatography and preparative HPLC. The overall yield from 8 litres of fermentation broth was 160 mg r‐hSP and 219 mg glycosylated r‐hSP corresponding to 50% and 34%, respectively. The structure of the r‐hSP and the glycosylated r‐hSP was determined by amino acid analysis and carbohydrate composition analysis as well as by peptide mapping, amino acid sequencing and mass spectrometric analysis.

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