The peptide way to macrocyclic bifunctional chelating agents: synthesis of 2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid and study of its yttrium(III) complex.

摘要: Monoclonal antibody technology allows the specificity of an for its antigen to be used in targeting cancer cells. The conjugation metals/emdash/particularly radionuclides such as /sup 90/Y or 67/Cu/emdash/ monoclonal antibodies results agents radiommunotherapy and other medical applications. Chelators that can hold radiometals with high stability under physiological conditions are essential avoid excessive radiation damage nontarget Macrocylic polyamines, key precursors macrocyclic bifunctional chelating agents, synthesized by bimolecular cyclizations. Competition between polymerization desired cyclization is a common problem; authors efforts form 12-membered macrocycle cyclizations gave unsatisfactory yields. They have developed new synthetic route these macrocycles via peptide synthesis intramolecular tosylamide ring closure. For polyazamacrocyles nitrogens separated two-carbon chains, peptides made from /alpha/-amino acids readily accessible starting materials. Treatment borane converts linear polyamino alcohols, which original backbone has been converted C-terminal alcohol, N-terminal primary amine, internal secondary amines (Figure 1, step 1). p-toluenesulfonyl chloride produces tosyl ester, tosylamide, tertiary tosylamides. mild base nucleophliemore » displaces ester thus forms yield. This cyclication may performed very dilute solution, eliminating concerns about polymer formation.« less