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Synthesis of a New Bivalent Hirudin Analog (hirufos), which includes a stable 4′‐phosphono‐ L ‐phenylalanine mimic of ( L ‐tyrosine O 4 ‐sulfate)‐63
Author(s) -
Thurieau Christophe,
Guyard Christel,
Simonet Serge,
Verbeuren Tony J.,
Fauchère JeanLuc
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770311
Subject(s) - chemistry , tetrapeptide , hirudin , stereochemistry , phenylalanine , bivalent (engine) , conjugate , peptide , peptide synthesis , combinatorial chemistry , amino acid , biochemistry , organic chemistry , thrombin , mathematical analysis , platelet , mathematics , biology , metal , immunology
The synthesis on solid phase of a new derivative of the anticoagulant protein hirudin is described (see Scheme and Fig.1 , I ). The henicosapeptide is a bivalent conjugate of the C‐terminus of hirudin and of the active‐site‐binding tetrapeptide D ‐Phe‐Pro‐Arg‐Pro linked via a tetraglycine spacer. The peptide, for which the name hirufos was coined, incorporates a stable phosphono derivative of L ‐phenylalanine which, combined with the other structural modifications, leads to a potent anticoagulant agent. Synthesis was readily achieved by the (9 H ‐fluoren‐9‐yl)‐methoxycarbonyl (Fmoc) strategy followed by acidolytic cleavage from the resin and deprotection, including the liberation of the crucial phosphonic group on L ‐phenylalanine.