The study shows that the humanin peptide (especially a Ser14Gly version) is mostly floppy in plain water but folds a bit when placed in a salty buffer like PBS, especially at higher amounts and warmer temperatures. This folding is due to the peptide sticking to itself through water‑shunning (hydrophobic) forces. The normal humanin behaves the same way, but the concentrations needed to see these effects are much higher than what you'd find in the body.

The structure of a highly potent Ser14Gly analog of antiAlzheimer peptide, Humanin, was examined by circular dichroism (CD). The secondary structure is more disordered in water than in phosphate-buffered saline (PBS). The peptide structure in water is little dependent on both peptide concentration and temperature. On the contrary, the peptide structure was significantly different in PBS from the structure in water, which is more apparent at a higher peptide concentration and temperature. The observed different structure in PBS appears to be due to self-association of the peptide, which is enhanced by elevated temperature and, hence, via hydrophobic interactions. The wild-type Humanin also behaved similarly, i.e., it assumed a disordered structure in water but underwent conformational changes in PBS. Although high peptide concentrations for CD measurements are not encountered in vivo, the results suggest the tendency of the peptide to interact hydrophobically with other structures as well as with itself.