Convenient solid-phase synthesis of ureido-pyrimidinone modified peptides

Peptides have been modified with quadruple hydrogen bonding ureido-pyrimidinone moieties to be applied in supramolecular architectures for biomedical applications. A convenient solid-phase synthesis method was developed to functionalize peptide sequences with ureido-pyrimidinone units. Two different ureido-pyrimidinone synthons were used: based on a carbonyldiimidazole-activated amine or on an isocyanate functionality. Oligopeptides were functionalized on the solid support using two coupling strategies: on the N-terminus or selectively on the -position of a C-terminal lysine. Several peptides were modified to show the generality of the approach, varying from cell adhesion sequences, to collagen binding peptides and cysteine derivatives which can be used for native chemical ligation.