Adapted from: stability optimization of engineered mAbs
0
0.005
0.01
0.015
Ratio
First
Derivative
0.75
0.8
0.85
0.9
0.95
Ratio
350
nm
/
330
nm
30 40 50 60 70 80 90
Temperature [°C]
The original parent mAb is more stable
than its derivatives. However, all chil-
dren mAbs are close in T
m
value to their
parent
36BLX
35BLX
33BLX
34BLX
37BLX
Protein A-2
36BLX
35BLX
33BLX
34BLX
37BLX
Protein A-3
36BLX
35BLX
33BLX
34BLX
37BLX
Protein A
36BLX
35BLX
33BLX
34BLX
37BLX
Protein A-1
36BLX
35BLX
33BLX
34BLX
37BLX
Protein A-4
When engineering antibodies
or other therapeutic proteins,
even a few point mutations
result in major changes to the
protein unfolding profile.
Here is shown a parent mAb
(purple) and four child mAbs
that differ from the parent by
2-3 single amino acid changes.
The thermal unfolding profile
changes — not only the T
m
,
but also its overall shape —
demonstrating what a dramatic
impact mutations have on
thermal stability.
