DOTA-tris(OPp ester) as a bifunctional prochelator for the preparation of DOTA-peptide conjugates

Peptides containing the chelator DOTA have gained importance for molecular imaging and therapy with radionuclides. However, all synthons described for the convergent solid phase synthesis of DOTA-peptide conjugates show windows of stability that are too narrow to allow a clean and convergent deprotection process. The synthesis of the new prochelator DOTA-tris(OPp ester) starting from cyclen is reported. Using this prochelator for the synthesis of several DOTA peptide conjugates revealed that its cleavage-in contrast to the cleavage of DOTA-tris(tBu ester) conjugates-does not require an extended deprotection time, and therefore results in clean and homogenous products.