I am trying to solubilize a peptide:oligonucleotide conjugate for intra-peritoneal injection into a mouse. At low concentrations, the mixture dissolves nicely in either H2O or saline, however at higher concentrations, everything crashes out. The peptide is hydrophobic but both the peptide and oligonucleotide are currently dissolved at very high (stock) concentrations in HBSS or TE.
I just tried Ethanol (10 and 50%), DMSO (10 and 50%), PEG-400 (10 and 50%) and Glycerol (50%). The saline and glycerol generally keep most of the protein:olgo conjugate in solution, but the others generate large solid pellets in the bottom of the tube after 30 minutes at room temperature.
Can anyone advise on other possible solvents to try?
Have you tried starting with DMSO and then adding the water/buffer?
You also could try adding polyamines (e.g. spermidine or shorter poly-lysines/poly-arginines/poly-ornithines) to compensate for the negative charges of the DNA. For more sophisticated approaches, and some background information, please check this brochure: https://media.iris-biotech.de/flyers/IF20_2_Polymer_Therapeutics.pdf
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