TY - JOUR
TI - Unveiling and tackling guanidinium peptide coupling reagent side reactions towards the development of peptide-drug conjugates
AU - .I. Vrettos, N. Sayyad, E.M. Mavrogiannaki, E. Stylos, K.D. Androniki, S. Papas, T. Mavromoustakos, V. Theodorou, A.G. Tzakos
JO - RSC Advances
PY - 2017
VL - 7
TODO - 80
SP - 50519-50526
PB - Royal Society of Chemistry
SN - 2046-2069
TODO - 10.1039/c7ra06655d
TODO - -
TODO - Peptide coupling reagents and especially uronium/guanidinium salts have been extensively utilized in solidphase peptide synthesis. However, the impact of these reagents in solution phase synthesis, normally used
in the formation of peptide-drug conjugates (PDCs), has not been fully explored. Herein, we identified that
when guanidinium salts are used in classical peptide coupling conditions, besides leading to the formation
of amide bonds, a uronium derivative can also be installed on specific amino acid scaffolds. The formation of
this side product depends on the reaction conditions, as also on the nucleophilicity of the susceptible
groups. Conditions to avoid this side product formation and a putative reaction mechanism describing its
formation are reported.
ER -