Antimicrobial activity peptides

R527 D. J. Schibli and H. J. Vogel, Structural Studies of Lactoferricin B and its Antimicrobial Active Peptide Fragments , Int. Congr. Ser., 2000, 1195, 27... 

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-... 

Zasloff, M., Martin, B., and Chen, H -C. Antimicrobial activity of synthetic ma-gainin peptides and several analogues. Proc. Natl. Acad. Sci. USA 1988, 85, 910-913. 

Research activity in this area has mainly concentrated on the design and in vitro studies of amphiphihc helical /9-peptides with antimicrobial activity. In view of their high propensity for helical conformations as well as their resistance to proteolytic degradation, /9-peptides represent promising antibacterial candidates. 

Fig. 2.40 Sequences and helical wheel representation of amphiphilic 2.5,2-helical jS-pep-tide 17-mers evaluated for antimicrobial activity [234, 248]. These peptides are exclusively composed of hydrophobic trans-ACPC...

In another study, the carrier protein was replaced by an enzyme compatible solid-phase resin (PEGA), and enzyme-catalyzed cyclization was used to probe substrate specificity. This study demonstrated also that oxo-esters are tolerated as substrates for TE domains, and then-preparation in library format served as an excellent tool for substrate specificity studies, as well as for preparation of cyclized peptides. Figure 13.11 shows how the TycA TE showed selectivity for only residues 1 and 9 (colored in red), and changes at all other residues were tolerated [42]. Hydrogen bonding interactions are shown in green. Several compounds made from this series were shown to demonstrate improved therapeutic indices (with respect to hemolysis) while retaining antimicrobial activity. 

Keywords Solid-state NMR structure analysis 19F-labeling Membrane-active peptides Native biomembranes Oriented membrane models Antimicrobial peptides... 

Direct Antimicrobial Activity of Host Defense Peptides In Vivo 191... 

In addition to the cathelicidins and defensins, humans also utilize a variety of other host defense peptides. Examples of these include the anionic dermcidins, found in human sweat and possessing potent antimicrobial activity in a broad range of pH and salt concentrations, and the histatins, a histidine-rich host defense peptide family found in humans and higher primate species. The histatins are normally found in saliva and utilize an alternative mechanism to bacterial membrane lysis for their antimicrobial activity. ... 

It has also been demonstrated that the transmembrane potentials of prokaryotes are typically 50% greater than their eukaryotic counterparts. This chemiosmotic potential has been proposed to act electrophoretically on host defense peptides attached to the microbial surface. It should also be noted that although increased cationicity of the host defense peptides is generally associated with increased antimicrobial activity there is a threshold by which selectivity between host and microbial cells is lost at the behest of increased cationicity. 

Structure-Activity Relationship Studies of the Antimicrobial Activities of the Host Defense Peptides... 

Structure-activity relationship studies investigating the antimicrobial activities of host defense peptides have primarily sought the characterization of the specific sequence/structural motifs that dictate antimicrobial and cytotoxic activities. Perhaps unsurprisingly these activities appear to be dictated by a delicate balance of cationicity, hydrophobicity, amphipathicity, and ultimately the structural characteristics of the peptides. 

Thus, the optimization of the antimicrobial activity and minimization of cytotoxicity associated with host defense peptides through natural or synthetic means require the balance of a variety of physicochemical properties rather than the optimization of a single attribute. 

---