There are probably two possibilities:

1. The peptide aggregates in DPC, causing the formation of large mixed peptide micelles that are invisible to NMR. If this is the case, the whole 1H spectrum should have disappeared including the residual DPC peaks. DLS can also give you conformation that large mixed micelles are present. This is not uncommon with cationic peptides that do not adopt secondary structure upon membrane binding (see for example

https://www.researchgate.net/publication/237930385_The_Sevi_Precursor_Peptide_PAP248-286_a_Dramatic_Enhancer_of_HIV_Infectivity_Promotes_Lipid_Aggregation_and_Fusion?ev=prf_pub

If this is the problem, try adding the detergent to the peptide above the CMC immediately. Free detergent below the CMC may be the cause of the aggregation.

If this doesn't work,there isn't an easy answer to this problem except to try another detergent.

2. The peptide binds the micelle in the intermediate time-scale which leads to broadening of the peaks. In this case, the peptide should have a broadened signal but the residual DPC peaks should be sharp (most of the DPC molecules should not be participating in exchange). You may have to add some protonated DPC to see the peaks. If this is the problem you can try the following to shift the on/of rate to move the timescale into either a slower or faster region to get a better spectrum:

1. Change the temperature

2. Add more DPC (keep above CMC)

3. Go to a different field spectrometer (since the relevant timescale depends on the magnetic field)

4. Add NaCl

Article The Sevi Precursor Peptide PAP248-286, a Dramatic Enhancer o...