Evaluation of Substituted N-Aryl Maleimide and Acrylamides for Bioconjugation

Novel SF5-bearing maleimide and acrylamide derivatives were synthesised as potential [18F]radio-prosthetic groups for radiolabelling peptides proteins. The efficacy of selected prosthetic was first assessed through bioconjugation with protected model amino acid derivatives. These reactions investigated on an analytical scale via LC-MS across a pH range to quantitatively evaluate this group’s reactivity stability. Model bioconjugate then replicated using analogous para-substituted determine the influence electronic effects -SF5. Finally, utilised cancer-targeting c-RGD peptides. N-aryl maleimides reacted extremely efficiently N-acetyl-L-cysteine. subsequent conjugates obtained regio-isomeric mixtures corresponding thio-succinamic acids in yields 80–96%. Monitoring reaction by revealed that ring hydrolysis intermediate SF5–thio-succinimide conjugate occurred instantaneously, advantageous quality minimising undesirable thiol exchange non-targeted cysteine residues. In contrast, acrylamides demonstrated poor solubility semi-aqueous media (<1 mM). turn, synthetic-scale bioconjugations Nα-acetyl-L-lysine performed methanol, affording modest high yield (58–89%). Including electron-deficient, fluorinated will broaden their applicability within fields 19F-MRI PET imaging.