Peptide antibacterial activities

As such, the magainins provide a useful initial target for peptoid-based peptido-mimetic efforts. Since the helical structure and sequence patterning of these peptides seem primarily responsible for their antibacterial activity and specificity, it is conceivable that an appropriately designed, non-peptide helix should be capable of these same activities. As previously described (Section 1.6.2), peptoids have been shown to form remarkably stable hehces, with physical characterishcs similar to those of peptide polyprohne type-I hehces (e.g. cis-amide bonds, three residues per helical turn, and 6A pitch). A faciaUy amphipathic peptoid helix design, based on the magainin structural motif, would therefore incorporate cationic residues, hydrophobic aromatic residues, and hydrophobic aliphathic residues with threefold sequence periodicity. 

Tab. 2.9 Antibacterial activities of [Ala ]-magainin II amide and amphiphilic 3i4-helical ent-157b, 83-85) and 2.5,2-helical (158, 159) yS-peptides [175, 234, 248]...

Salick DA, Kretsinger JK, Pochan DJ et al (2007) Inherent antibacterial activity of a peptide-based beta-hairpin hydrogel. J Am Chem Soc 129 14793-14799... 

Casein-derived phosphorylated peptides are believed to enhance the bioavailability of calcium from milk and dairy products (Pihlanto and Korhonen, 2003), and a phosphopeptide derived from (3-casein has been shown to increase iron bioavailability (Bouhallab et ah, 2002 Peres, 1999). Other casein-derived peptides have been found to contain antihypertensive activity in rats (Leclerc et ah, 2002 Miguel et ah, 2009). A number of casein fragments demonstrate antibacterial activity (Kilara and Panyam, 2003). 

Cytolycin. Cytolycin is a two-peptide lantibiotic that is produced by E. faecalis strains. In this context, it is interesting to note that though cytolycin is a cytolytic/hemolytic peptide, it also encompasses a strong antibacterial activity and is therefore often referred to as a bacteriocin. The regulation of cytolycin... 

Altematamides A-C (92-94), bromotryptamine peptides from the Atlantic bryozoan Amathia alternata, show modest antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis,... 

Dialkyl 1-aminoalkanephosphonates, which are moieties in peptide analogues, with antibacterial activity, and important inhibitors of aminopeptidases330 have been synthesised from oximes in THF (equation 81)331. 

Another cyclic peptide, halobacillin, was isolated from a marine-derived Bacillus sp. isolated from a deep-sea sediment core.31 Halobacillin (Structure 18.21) was only produced in sea-water-based media and is similar in structure to the surfactins and iturins. Interestingly, the compound exhibits cytotoxicity against the human colon tumor cell fine HCT-116 but lacks the antibacterial activity associated with surfactin. 

A QSAR seeks to relate quantitative properties (descriptors) of a compound with other properties such as drug-like activity or toxicity. The essential assumption of QSAR is that quantities that can be conveniently measured or calculated for a compound can be used to accurately predict another property of interest (e.g., antibacterial activity) in a nontrivial way. QSAR has become an integral part of screening programs in pharmaceutical drug-discovery pipelines of small compounds and more recently in toxicological studies (69). However, the use of QSAR modeling applied to the search for antimicrobial peptides is relatively recent. Advances in this area are reviewed in brief here. 

There are two separate but interrelated aspects to QSAR modeling of antibacterial peptides the choice of QSAR descriptors and the choice of numerical analysis techniques used to relate these values to antibacterial activity. A simple example of a QSAR descriptor is the total charge of a peptide. A large number of QSAR descriptors is available for small compounds in the literature and from commercial software products that may be considered. A smaller subset is used in QSAR studies of antibacterial peptides and may be separated into two categories descriptors based on empirical values and calculated descriptors. An example of an empirical value is HPLC retention time, which is a surrogate measure of solubility or hydrophilicity/hydrophobicity. An example of a calculated descriptor is total peptide charge at pH 7. 

Mandal, M., Jagannadham, M.V. and Nagaraj, R. (2001) Antibacterial activities and conformations of bovine (3-defensin BNBD-12 and analogs structural and disulfide bridge requirements for activity. Peptides 23,413 118. 

Selsted, M.E., Tang, Y.-Q., Morris, W.L., et al. (1993) Purification, primary structures, and antibacterial activities of b-defensins, a new family of antimicrobial peptides from bovine neutrophils. J. Biol. Chem. 268, 6641-6648. 

Shi, J., Ross, C.R., Chengappa, M.M., Sylte, M.J., McVey, D.S., and Blecha, F. (1996) Antibacterial activity of a synthetic peptide (PR-26) derived from PR-39, a praline-arginine-rich neutrophil antimicrobial peptide. Antimicrob. Agents Chemother. 40, 115-121. 

In 1960, Ramseier [22] discovered that nisin causes leakage of intracellular molecules from cells. Later, it was shown that it disturbs the membrane potential and interferes with energy transdudion [23]. In addition, it causes inhibition of biosynthesis of the cell wall processes by blocking the synthesis of peptidoglycans [24] and by binding to the precursor lipid II [25]. However, micromolar amounts of nisin are needed to permeate artificial membranes [26,27] or to inhibit cell wall synthesis in vitro [28], while the in vivo activity of nisin is in the nanomolar range. As vancomycin, which binds to the peptide motif in lipid II, inhibited the antibacterial activity and... 

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