Overview

Melittin is able to bind to plasma membranes by way of electrostatic interactions between melittin’s positively-charged C-terminus and the negatively-charged phospholipid bilayer of cells, as has been demonstrated by previous research (Hall et al., 2010).  In this section, we will examine how altering the amino acid sequence at the C-terminus of melittin has important implications not only for plasma membrane affinity, but also for anticancer activity.

Anticancer Activity: Using Bioengineered DEDE-Melittin as a Research Tool

Bioengineering technology allowed researchers the unique opportunity to study the importance of the positively-charged C-terminus of melittin, by way of using DEDE-melittin in which this positive charge was reversed.  It was determined that DEDE-melittin demonstrated no anticancer activity on either HER2-enriched breast cancer cells or TNBC cells, which signifies that the positive charge normally at the C-terminus plays an important role in terms of bringing about toxic effects in breast cancer cells.

To verify this highly significant finding, researchers rescued the positive charge at the C-terminus by using SV40-melittin.  As expected, anticancer activity was recovered when this variant was tested on T11 cells.  Nevertheless, it should be noted that, in this particular situation, size matters; by also studying TAT-melittin, researchers discovered that any larger of a positive sequence at the C-terminus decreases the anticancer properties of melittin.

a: The impact of DEDE-melittin on the cell viability of both HER2-enriched breast cancer cells (SKBR3) and TNBC cells (SUM159).  b: Comparing the impact of different melittin variants on the cell viability of squamous cell carcinoma cells (T11) (Duffy et al., 2020).

References