D-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution.

ABSTRACT: The residualizing prosthetic agent N^ε-(3-[^*I]iodobenzoyl)-Lys⁵-N^α-maleimido-Gly¹-d-GEEEK ([^*I]IB-Mal-d-GEEEK) showed promise for the radioiodination of monoclonal antibodies (mAbs) that bind to internalizing molecular targets. Although enhanced tumor uptake was achieved in these studies, elevated kidney accumulation also was observed, particularly with low-molecular-weight, single-domain antibody fragments (sdAbs). Here, we developed an analogous agent (IB-Mal-d-GDDDK), in which glutamate residues (E) were replaced with aspartates (D) to determine whether this modification could decrease renal uptake. [¹²⁵I]IB-Mal-d-GDDDK and [¹³¹I]IB-Mal-d-GEEEK were synthesized with similar radiochemical yields (60⁻80%) and c

SUBMITTER: Pruszynski M 

PROVIDER: S-EPMC6099567 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature