Could you be a bit more precise, please? Which molecules (spacers?) are you actually using, which solvents and coupling conditions? Maybe DBCO is too bulky.

Are there any solubility issues?

Wolfgang Schechinger

Thanks for the response.

I have azide modified SSDNA synthesized by a vendor, and I have DBCO modified Qdots. Let me know if you need more clarification.

Do you have some controls, e.g., some other azide and a DBCO conjugate that is coupled to a protein (in contrast to a charged oligo resp. the QDs)? In this way, you might be able to resolve the tricky component, e.g., by SDS-PAGE.

One thing that comes to my mind is a possible secondary structure of the DNA that is masking the azide. Adding formamide or a polyamine like e.g., spermidine, might help to resolve this.