Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues

Title:Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues

Volume: 16 Issue: 1

Author(s): Elaheh Jamasbi, Anna Mularski and Frances Separovic

Affiliation:

Keywords: Antimicrobial peptides, Cytotoxicity, Melittin, Melittin analogues, Membranes.

Abstract: Melittin is a 26 residue peptide and the major component of bee (Apis mellifera) venom. Although melittin has both anticancer and antimicrobial properties, utilization has been limited due to its high lytic activity against eukaryotic cells. The mechanism of this lytic activity remains unclear but several mechanisms have been proposed, including pore formation or a detergent like mechanism, which result in lysis of cell membranes. Several analogues of melittin have been synthesized to further understand the role of specific residues in its antimicrobial and lytic activity. Melittin analogues that have a proline residue substituted for an alanine, lysine or cysteine have been studied with both model membrane systems and living cells. These studies have revealed that the proline residue plays a critical role in antimicrobial activity and cytotoxicity. Analogues lacking the proline residue and dimers of these analogues displayed decreased cytotoxicity and minimum inhibition concentrations. Several mutant studies have shown that, when key substitutions are made, the resultant peptides have more activity in terms of pore formation than the native melittin. Designing analogues that retain antimicrobial and anticancer activity while minimizing haemolytic activity will be a promising way to utilize melittin as a potential therapeutic agent.

Cite this article as:

Jamasbi Elaheh, Mularski Anna and Separovic Frances, Model Membrane and Cell Studies of Antimicrobial Activity of Melittin Analogues, Current Topics in Medicinal Chemistry 2016; 16 (1) . https://dx.doi.org/10.2174/1568026615666150703115919