Solid‐phase synthesis of H‐ and methylphosphonopeptides
- 1 April 1996
- journal article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 47 (4) , 245-253
- https://doi.org/10.1111/j.1399-3011.1996.tb01352.x
Abstract
We introduce solid-phase syntheses of H- and methylphosphonopeptides, giving access for the first time to a new class of mimics for o-phosphoamino acids. The model peptides H-GlyGlyXaaAla-OH (Xaa = Ser, Thr) were synthesized on a solid-phase using Fmoc/tBu strategy and HBTU/HOBt activation by incorporation of hydroxyl-protected serine and threonine. As selectively cleavable hydroxyl-protecting groups we used triphenylmethyl and tert-butyldimethylsilyl for both amino acids, as described in the literature. All peptides were phosphitilated with O,O-di-tert-butyl-N,N-diethylphosphoramidite and yielded H-phosphonopeptides after trifluoroacetic acid cleavage. Alternatively we phosphonylated the peptides with O-tert-butyl-N,N-diethyl-P-methylphosphonamidite, which was synthesized by a two-step one-pot procedure starting from commercially available chemicals. All H- and methylphosphonopeptides were obtained in high purities and yields, as shown by reversed-phase high-performance liquid chromatography and anion-exchange chromatography. The phosphonopeptides were characterized by 1H and 31P NMR. We confirmed their molecular masses by electrospray mass spectrometry and analyzed their fragmentation schemes, which seemed to be characteristic for each class of analogues. The H-phosphonopeptides lost phosphonic acid (H3PO3, 82 mass units) and the methylphosphonopeptides lost methylphosphonic acid (MeH2PO3, 96 mass units). Both H- and methylphosphonopeptides represent a new and simply accessible class of mimics for phosphopeptides. Compared with the corresponding phosphopeptides all phosphonopeptides were synthesized in higher yields and purities (>80%). © Munksgaard 1996.Keywords
This publication has 30 references indexed in Scilit:
- Benzyloxy(diisopropylamino)methylphosphine: A Powerful Reagent for the Synthesis of MethylphosphonopeptidesSynthesis, 1995
- 1H and 31P NMR spectroscopy of phosphorylated model peptidesInternational Journal of Peptide and Protein Research, 1994
- Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatasesBiochemistry, 1992
- Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acidsInternational Journal of Peptide and Protein Research, 1990
- Ion spray interface for combined liquid chromatography/atmospheric pressure ionization mass spectrometryAnalytical Chemistry, 1987
- PROTEIN SERINE/THREONINE KINASESAnnual Review of Biochemistry, 1987
- MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopyJournal of Magnetic Resonance (1969), 1985
- Coherence transfer by isotropic mixing: Application to proton correlation spectroscopyJournal of Magnetic Resonance (1969), 1983
- The effect of phosphorylation of the histidyl residue in the tetrapeptide Gly‐Gly‐His‐Ala. Changes of chemical shift and pK values in 1H‐ and 31P‐NMR spectraMagnetic Resonance in Chemistry, 1981
- 1H‐nmr parameters of the common amino acid residues measured in aqueous solutions of the linear tetrapeptides H‐Gly‐Gly‐X‐L‐Ala‐OHBiopolymers, 1979