The same candidate displays very different thermal
unfolding behaviors depending on its buffer environment.
Here, nanoDSF unveils the impact three different buffers
have on Herceptin
TM
, a cancer-targeting monoclonal
antibody therapeutic.
Lower pH buffer destabilizes T
m1
Increasing NaCl concentration further destabilizes Herceptin
Lower pH buffer stabilizes T
m2
/T
m3
, which reduces aggregation propensity
Temperature (°C)
First derivative
30 40 50 60 70 80 90
0.007
0.006
0.005
0.004
0.003
0.002
0.001
0
-0.001
PBS pH 7.4
25 mM Sodium Acetate pH 4.0
25 mM Sodium Acetate pH 4.0 + 130 mM NaCl
*Learn more about the impact of pH on colloidal stability in this app note
Note that lower pH has a tradeoff, where conformational
stability is decreased but colloidal stability is increased*.
While conformational stability from thermal unfolding
is a valuable first-pass tool for screening, keep in mind
there are other methods for evaluating stability, and it is
o en necessary to balance them.
