Synthesis and Evaluation of a Non-Peptide Small-Molecule Drug Conjugate Targeting Integrin α_Vβ₃.

ABSTRACT: An integrin α_Vβ₃-targeting linear RGD mimetic containing a small-molecule drug conjugate (SMDC) was synthesized by combining the antimitotic agent monomethyl auristatin E (MMAE), an enzymatically cleavable Val-Ala-PABC linker with a linear conjugable RGD mimetic. The structure proposal for the conjugable RGD mimetic was suggested upon the DAD mapping analysis of a previously synthesized small-molecule RGD mimetic array based on a tyrosine scaffold. Therefore, a diversifying strategy was developed as well as a novel method for the partial hydrogenation of pyrimidines in the presence of the hydrogenolytically cleavable Cbz group. The small-molecule RGD mimetics were evaluated in an ELISA-like assay, and the structural relationships were analyzed by DAD mapping revealing

SUBMITTER: Paulus J 

PROVIDER: S-EPMC9035832 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature