Cationic peptides antibacterial

Cationic peptides were traditionally isolated from natural sources or synthesized fay solid phase or solution phase chemistry. Moreover, they have recently been synthesized by recombinant DNA methods in bacteria (1). insect cells (2), and plants (3,4). The hta that cationic peptides are produced naturally by certain bacteria (e.g., see Qiapter 17), as well as the newly discovered ability to synthesize virtually any peptide by recombinant means in bacteria (1), clearly merits the use of the term "antibiotic for these compounds. Thus, cationic peptides represent not only the first new class of antibiotic in the past 30 yeais, but the world s first genetically engineeriitg antibacterials. 

The magaiitins are a class of hnear, cationic, faciaUy amphipathic and hehcal antibacterial peptides derived from frog skin [51]. The magaiitins exhibit highly selective and potent antimicrobial activity against a broad spectrum of organisms [52, 53]. As these peptides are faciaUy amphipathic, the magainins have a cationic heli-... 

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. 

The first edition of Food Analysis by HPLC fulfilled a need because no other book was available on all major topics of food compounds for the food analyst or engineer. In this second edition, completely revised chapters on amino acids, peptides, proteins, lipids, carbohydrates, vitamins, organic acids, organic bases, toxins, additives, antibacterials, pesticide residues, brewery products, nitrosamines, and anions and cations contain the most recent information on sample cleanup, derivatization, separation, and detection. New chapters have been added on alcohols, phenolic compounds, pigments, and residues of growth promoters. 

Debnath S, Shome A, Das D et al. Hydrogelation through self-assembly of Fmoc-peptide functionalized cationic amphiphiles potent antibacterial agent. J Phys Chem B 114 4407-4415... 

Al-Badri and co-workers [55] studied the effect of fine-tuning the cationic parameter of synthetic mimics of antimicrobial peptides (SMAMP) on haemolytic and antibacterial activities. A category of novel norbornene monomers that carry one, two or three Boc-protected amine-functionalities was synthesised (Figure 3.8). ROMP of the monomers, followed by deprotection of the amine groups led to cationic antimicrobial polynorbornenes that carry one, two and three charges per monomer repeat unit. It was observed that enhancing the number of amine groups on the most hydrophobic polymer effectively decreased its haemolytic activity. 

DeGrado and co-workers [59] first reported the de novo design of amphipathic, cationic, monosubstituted P-peptides as antibacterial complexes against the Gramnegative bacterium K91 Escherichia coli. However, as potent as these P-peptide antibiotics are they exhibited low selectivity for bacteria, as confirmed by extensive mammalian RBC lysis (haemolysis). A mainly stable secondary structure formed by P-peptides is the L+2 helix (also known as a 14-helix or a 31-helix (Figure 3.10). 

Small peptides are a promising class of antibacterial compounds. They are mostly comprised of cationic and lipophilic amino acids, and minimal motifs containing only Arg and Trp have been suggested. Presumably, interaction of these peptides with the bacterial cell membrane contributes to their activity. Assuming that metallocenes are bulky, lipophilic groups, which may (cobaltocenium) or may not (ferrocene) possess additional charges, we have... 

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