Toward the effective synthesis of bivalent Folate-targeted PEGylated cancer diagnostic and therapeutic agents using chemo-enzymatic processes

Abstract

This paper focuses on reviewing recent developments in folate-targeted cancer diagnostic agents. First clinical trials involving Small Molecule Diagnostic Conjugates (SMDCs) are discussed, followed by Polymer-based Folate-targeted Diagnostic Conjugates (PDCs). Specifically, the advantages of multivalent targeting are discussed. Finally, recent results of a new chemo-enzymatic approach for the synthesis of bivalent folate targeted, PEGylated PDCs is discussed. Unique feature is the use of monodisperse PEG (dPEG). This modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues.