Fig. 1.

Structure of siRNA conjugated JB577 peptide bound to the surface of the QD via a His₆ (Histidine) sequence. siRNA is conjugated to the positively charged VKIKK sequence by positive/negative charge interaction. The CdSe/ZnS QD is coated in negatively charged CL4 ligand occupying less space than polyethylene glycol (PEG)-derived ligands used by other investigators. WG is added to monitor the peptide during purification by HPLC and the palmitoyl group is N-linked to a modified cysteine (Dap) to mimic the native thiol linkage. Theoretical calculations for pH7.4 suggest the following properties of the different solubilizing coatings used: CL1 = +0.61−1.00 + 0 = −0.39 charge (one full negative charge) and a partially protonated amine complicated by the piperazine ring. CL2 = −0.04 net charge. Almost a full zwitterion, the amine is partially deprotonated. CL4 = +1.00−2.00 = −1.00 net charge. Two negative charges, one fully protonated amine, positive charge. PEGNH₂ = +0.9 net charge. One positive charge mostly fully protonated.