Antimicrobial Peptides for Detection and Diagnostic Assays - Designing Receptors for the Next Generation of Biosensors - page 86

selective toxicity has been suggested to be the phospholipid composition relevant to
the anionic character and net positive charge of the peptides [ 10 ].
While AMPs' antimicrobial action is apparent under in vitro conditions, micro-
bial killing is generally inhibited under physiological conditions among high
concentrations of monovalent ions, as well as in the presence of host and bacterial
proteases. However, the critical abilities of AMPs as effector molecules of the
immune system (i.e., the induction of wound repair, chemotaxis of for phagocytic
cells, and initiation of inflammatory responses) remain [ 11 ]. Under physiological
conditions, some AMPs have been shown to retain the ability to degrade microbial
biofilm, as well as inhibit other factors of virulence [ 12 ]. The ability of certain
peptides to bind LPS and LTA has also been implicated as their mechanism to
protect against sepsis [ 13 ]. A heptamer-peptide has been demonstrated as an
inhibitor of device-associated staphylococcal infection in rats [ 14 ], while numerous
studies have determined that structurally related peptides can have targets existing
beneath the cytoplasmic membrane as necessary antimicrobial mechanisms
[ 15 , 16 ]. AMPs have been shown to affect nucleic acid and protein synthesis,
inhibit enzymatic activity, and modulate genes related to virulence, such as biofilm
formation, motility, and secrete exotoxin without cell death [ 12 , 15 ].
AMPs are a unique and diverse group of molecules, which are categorized with
consideration of their synthesis, composition, and secondary structure. A prominent
group contains cationic peptides that are relatively short, lack cysteine residues, and
may have a proline hinge mid-sequence; this group is perhaps the best characterized
with respect to sequence, structure, and mechanisms of binding and killing.
In aqueous solutions, these peptides are generally disordered, seen in circular
dichroism as “random coil,” but in the presence of sodium dodecyl sulfate, phos-
pholipid vesicles, or LPS, the molecule takes on an a -helical conformation. The

percentage of -helicity seen in membrane models correlates with antimicrobial

activity against bacteria in vitro [ 17 , 18 ]. Included in this group are the magainins,
the cecropins, melittin, parasin, and the cathelicidins. The cathelicidins are a
diverse family of peptides and are identified based on a conserved N-terminal
domain of the peptide precursor [ 19 , 20 ]. Found in the granules of natural killer
lymphocytes, neutrophils, and in the epithelia of the skin, gut, and lungs, this class
of peptide is activated upon secretion by proteases [ 9 ].
A second group is comprised of cationic peptides that are rich in certain hydro-
phobic, charged, or aromatic residues. This group includes proline- and arginine-rich
peptides, such as the bactenecins and PR-39. Other notable members of this group are
indolicidin, which is rich in tryptophan residues and has a low net positive charge
(+3), and prophenin, which is rich in proline and phenylalanine residues. These
peptides lack cysteine residues and are linear and unstructured, or form extended
coils. While capable of binding to LPS [ 21 ], these peptides have a mode of antimi-
crobial action that is distinct from the classical model of cytoplasmic membrane
disruption; they are hypothesized to disrupt bacterial septum formation [ 15 ].
A third, large group comprises peptides that contain cysteine residues and form
stable

a

-sheets. This group includes protegrin, which forms toroidal pores as its
antimicrobial action [ 15 ] and the defensins. The

b

-defensins are produced by

a