Several cationic, amphipathic antimicrobial peptides or their derivatives have recently been reported with anticancer activity, displaying selective cytotoxicity against cancer cells in vitro and being effective in several in vivo xenograft models , , . Moreover, a recent report indicated a naturally occurring anticancer role of a host defense peptide, cathelicidin, in natural killer cells' antitumor functions in mice, most strongly supported by the experiment that cathelicidin knockout (Camp -/-) mice permitted faster tumor growth than wild type controls . All these findings suggest that these cationic, amphipathic peptides, which are used by nature in host defense, represent a very interesting and promising group of candidates to be developed for anticancer applications.
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Antimicrobial peptides, also known as host-defense peptides, represent a class of naturally occurring compounds that have recently been explored for their anticancer activity , , , , . Natural products have been playing an important role in developing chemotherapeutics with a substantial amount of anticancer agents in use being either natural or derived from natural products from various sources . Antimicrobial peptides are evolutionarily ancient weapons found throughout the animal and plant kingdoms . A hallmark of this class is that the molecule can adopt a structure in which clusters of cationic and hydrophobic residues are spatially organized in discrete sectors, and this cationic, amphipathic structural feature is critical for their activity and selectivity . Most host-defense peptides are believed to be membranolytic, with cationic residues selecting for anionic cellular membranes via electrostatic interactions and hydrophobic regions responsible for membrane permeation and disruption . Magainin 2 and its analogs were first found in 1993 to display selective cytoxicity towards carcinoma cells in vitro and were proven to be as effective as doxorubicin in vivo via intraperitoneal delivery in ovarian cancer mouse models . Over the last two decades, a growing number of studies have shown that some cationic, amphipathic peptides, including both natural host defense peptides and synthetic antimicrobial peptides, exhibit a broad spectrum of cytotoxic activity against cancer cells and are effective in reducing tumor burdens in several cancer animal models , , , , . The selectivity of these peptides towards cancer cells is not well understood and is hypothesized to result from some altered membrane properties of cancer cells compared to normal tissue cells, e.g., more negative charges on outer membrane leaflets, more microvilli, higher transmembrane potentials, or higher membrane fluidity , , , , .
Glossary | Linus Pauling Institute | Oregon State University
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The direct antimicrobial properties of small cationic peptides are often eliminated in the presence of physiologically relevant concentrations of serum and salt; thus they are more accurately described as host defence peptides.
Design, Synthesis and Biological Activity of Small ..
The net positive charge on the polar face is important for the antimicrobial and hemolytic activities of antimicrobial peptides . We constructed K11 by changing S to K at position 11 on the polar face of S16. This one addition to the net charge resulted in K11 showing the best biological properties among the tested peptides.
11/08/2017 · Abstract
This thesis deals with the design and synthesis of a library of α-aminoboronic di- andtri- peptides and investigation of their biological activity against different bacteria strains,fungi and kinases in order to discover compounds that can further be developed into drugs.