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