Cationic peptides structural classes

The improved DNA binding and condensation provided by amino acids such as tryptophan suggests that the inclusion of hydrophobic interactions within DNA complexes may be beneficial. Peptides with moities that provide cooperative hydrophobic behavior of alkyl chains of cationic lipids would improve the stability of the peptide-based DNA delivery systems. Two general classes of lipopeptide analogs of Tyr-Lys-Ala-Lysn-Trp-Lys peptides have been prepared by including a hydrophobic anchor. The general structures are N, N-dialkyl-Gly-Tyr-Lys-Ala-Lysn-Trp-Lys and Na,Ne-diacyl-Lys-Lysn-Trp-Lys. These peptides differ from the parent structures in that they self-associate to form micelles in aqueous solutions. The inclusion of dialkyl or diacyl chains in the cationic peptides improves the peptide ability to bind DNA and reduces aggregation of the complexes in ionic media. 

Recently, we reviewed the natural cationic peptides in depth and identified 145 sequences that have been isolated from nature (5). Some of these are listed according to structural class in Tables I and 2. Cationic peptides are ubiquitous in nature they have been identified in bacteria, fungi, plants, insects, cnistaceans, amphibians, mammals, and humans. 

One important milestone in our research is the design and development of new amino acid-based surfactants with antimicrobial properties, which mimic natural amphiphilic cationic peptides [42,43]. To this end, Lys and Arg derivatives of long-chain A -acyl, COO-ester, and A-alkyl amide have been prepared. In particular, the A -acylarginine methyl ester derivatives series 1 (Scheme 1) have turned out to be an important class of cationic surface active compounds with a wide bactericidal activity, high biodegradability, and low toxicity profile. We have shown that essential structural factors for their antimicrobial activity include both the length of the fatty residue (akin with their solubility and surface activity) and the presence of the protonated guanidine function [43,44]. 

Cell-penetrating peptides (CPPs) are a class of short, often cationic peptides that have the capability to translocate across cellular membranes, and although the translocation most likely involves several pathways, they interact directly with membranes, as well as with model bilayers. A review focuses on solution NMR as a tool for investigating CPP-lipid interactions. Structural propensities and cell-penetrating capabilities can be derived from a combination of CPP solution structures and studies of the effect that the peptides have on bilayers and the localization in a bilayer. 

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