jo0343432_si_001.pdf (3.02 MB)
Download fileSolid-Phase Functionalization of Peptides by an α-Hydrazinoacetyl Group
journal contribution
posted on 2003-08-15, 00:00 authored by Dominique Bonnet, Cyrille Grandjean, Pierre Rousselot-Pailley, Pascal Joly, Line Bourel-Bonnet, Valérie Santraine, Hélène Gras-Masse, Oleg MelnykA novel procedure for the preparation of α-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 BocNHNHCH2CO2H but could be minimized
with the diprotected derivative BocNHNH(Boc)CH2CO2H 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.