Solid Phase On-Peptide Synthesis of a Novel Cell Penetrating Molecular Probe for Cell Imaging and Drug Delivery

A modular solid phase multicomponent reaction for the synthesis of 3-substituted isoindolinone derivatives has been carried out. A mixture of a chiral -keto lactam, an aldehyde, an isocyanide and a dienophile react to produce chiral 3-substituted isoindolinones in one pot. Modularity has been accomplished by using solid supported aldehydes and dienophiles. Optimiza-tion was achieved by using microwave as the source of energy. The reaction was also performed on a biologically relevant pro-apoptotic peptide D(KLAKLAK)2 on solid phase. The molecules show significant fluorescence with large Stokes shifts and fast cell penetration. The chimeric peptides can be tracked under microscope proving the potential of the probes as cell sensors and were efficiently internalized as compared to non-labeled peptide, with a concomitant induction of apoptosis proving their potential as drug carriers.