Melittin-like peptide

This was the basis for the development of a second generation DPC, named ARC-520, which is currently in phase II clinical trial for the treatment of hepatitis B (Table 14.2). In ARC-520, the previous endosomolytic PBAVE polymer was replaced with a melittin-like peptide (MLP) with a well-defined structure. In addition, there is no chemical link between the siRNA and the polymer. Thus, ARC-520 consists of two individual components cholesterol-siRNA conjugates and hepatocyte-targeting membrane-active peptides linked to the MLP polymer. 

THOMPSON SA, TACHiBANA K, NAKANisHi K, KUBOTA I. Melittin-like peptides from the shark-repelling defense secretion of the sole Pardachirus pavoninus. Science 1986 Jul 18 233(4761) 341-3. 

IKCNCKRHVl KPHICRKICG KNa (disulfide bonds C -C /C -C ), a cationic 22-peptide amide. MCDP is a component of the bee venom which contains several biologically active non-peptide substances, as weU as two more major peptides, the hemolytic peptide melittin, the neurotoxic peptide apamin, together with a number of minor peptides. like apamin, MCDP blocks Ca -dependent K channels in neurons. MCDP causes mast cell degranulation and histamine release at low concentrations, and has anti-inflammatory activity at higher concentrations [E. M. Dotimas et al., Biochim. Biophys. Acta 1987, 911,285 W. E. Steinmetz et al.. Peptide Res. 1994, 7,77 A. Buku, Peptides 1999,20,415]. 

Analysis of melittin-induced conductance fluctuations suggests perturbations of the lipid bilayer structure, and formation of structural channels. Addition of pronase to the trans-side in the presence of a trans-negatiwe membrane potential abolished the conductance as it did when added to the cis side. This implies that the conducting state of melittin requires a trans-membrane configuration. In a non-conducting absorbed state a hydrophobic loop, with the region from threonine-9 to proline-13 as the likely site of the turn, penetrates the lipid but does not extend across the membrane. In the conducting state the turn becomes extended as the peptide assumes a rra w-bilayer position. 

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