Solid-phase functionalization of peptides by an alpha-hydrazinoacetyl group.
A novel procedure for the preparation of alpha-hydrazinoacetyl peptides is reported on the basis of the solid-phase coupling of partially or fully Boc-protected hydrazino acetic acid derivatives. The degree of unwanted polymerization of the activated ester during both activation and coupling was found to be significant for the monoprotected derivative BocNHNHCH(2)CO(2)H but could be minimized with the diprotected derivative BocNHNH(Boc)CH(2)CO(2)H and suppressed with the fully protected acid. Despite the instability of the imidocarbonate group toward acids and bases, a low-cost and effective route was sought for the preparation of the tris(Boc)-protected derivative. The N,N,N'-tris(Boc)hydrazinoacetic acid could be introduced on the solid phase after or before peptide elongation using Fmoc/tert-butyl chemistry. In this latter case, HR MAS NMR analysis of model solid supports demonstrated the partial loss of one Boc group during the repetitive piperidine treatments. Despite this slight instability, N,N,N'-tris(Boc)hydrazinoacetic acid was found to be a highly convenient reagent for the robust and easily scalable preparation of hydrazinopeptides in good yield and high purity.
Bonnet
Dominique
D
UMR CNRS 8525, Biological Institute of Lille, 1 rue du Pr Calmette, 59021 Lille, France. dominique.bonnet@sedac-therapeutics.com
Grandjean
Cyrille
C
Rousselot-Pailley
Pierre
P
Joly
Pascal
P
Bourel-Bonnet
Line
L
Santraine
Valérie
V
Gras-Masse
Hélène
H
Melnyk
Oleg
O
D000595:Amino Acid Sequence; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*
D006834:Hydrazines; D007202:Indicators and Reagents; D010455:Peptides