Synthesis and Biological Evaluation of RGD and isoDGR-Monomethyl Auristatin Conjugates Targeting Integrin α_V β₃.

ABSTRACT: This work reports the synthesis of a series of small-molecule-drug conjugates containing the α_V β₃ -integrin ligand cyclo[DKP-RGD] or cyclo[DKP-isoDGR], a lysosomally cleavable Val-Ala (VA) linker or an "uncleavable" version devoid of this sequence, and monomethyl auristatin E (MMAE) or F (MMAF) as the cytotoxic agent. The conjugates were obtained via a straightforward synthetic scheme taking advantage of a copper-catalyzed azide-alkyne cycloaddition as the key step. The conjugates were tested for their binding affinity for the isolated α_v β₃ receptor and were shown to retain nanomolar IC₅₀ values, in the same range as those of the free ligands. The cytotoxic activity of the conjugates was evaluated in cell viability assays with α

SUBMITTER: Raposo Moreira Dias A 

PROVIDER: S-EPMC6593765 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature