Fmoc/solid-phase synthesis of Tyr(P)-containing peptides through t-butyl phosphate protection.
The synthesis of Tyr(P)-containing peptides by the use of Fmoc-Tyr(PO3Me2)-OH in Fmoc/solid phase synthesis is complicated since, firstly, piperidine causes cleavage of the methyl group from the -Tyr(PO3Me2)-residue during peptide synthesis and, secondly, harsh conditions are needed for its final cleavage. A very simple method for the synthesis of Tyr(P)-containing peptides using t-butyl phosphate protection is described. The protected phosphotyrosine derivative, Fmoc-Tyr(PO3tBu2)-OH was prepared in high yield from Fmoc-Tyr-OH by a one-step procedure which employed di-t-butyl N,N-diethyl-phosphoramidite as the phosphorylation reagent. The use of this derivative in Fmoc/solid phase peptide synthesis is demonstrated by the preparation of the Tyr(P)-containing peptides, Ala-Glu-Tyr(P)-Ser-Ala and Ser-Ser-Ser-Tyr(P)-Tyr(P).
Perich
J W
JW
Biochemistry and Molecular Biology Unit, School of Dental Science, University of Melbourne, Victoria, Australia.
Reynolds
E C
EC
D000595:Amino Acid Sequence; D000596:Amino Acids; D005449:Fluorenes; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010755:Organophosphates; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D019000:Phosphotyrosine; D014443:Tyrosine / Q000031:analogs & derivatives*
D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010755:Organophosphates; D010455:Peptides; D019000:Phosphotyrosine; C071068:tert-butyl phosphate; D014443:Tyrosine