Designing Recognition Elements for Biomolecules: A New Class of Antibiotics.
- The emergence of many strains of multidrug-resistant bacteria, coupled with the new
threat of bio-terrorism, has led to a renewed interest in the generation of novel
types of antimicrobial therapeutics against the CDC Category A-C bacterial strains.
- One such potential new therapeutic that has recently garnered interest is the class
of antimicrobial cationic peptides. Part of the innate immune system of such diverse
organisms as plants, invertebrates, and vertebrates, antimicrobial peptides exhibit
a broad spectrum of activity against Gram-positive and Gram-negative bacteria by binding
to and disrupting bacterial cell wall components. Significantly, bacteria have not
developed resistance to these peptides.
- However, use of the native cationic peptides as therapeutic agents is problematic,
for they are expensive to produce in sufficient quantity, are unstable to endogenous
proteases, and host effects are substantial, including toxicity.
- Our group is preparing synthetic anion receptors that will have high affinity for
bacterial membrane anionic phospholipids (these phospholipids are highly hydrated,
and the receptor may benefit from the ability to incorporate water into its binding
motif see other project).
- The linkage of these receptors to membrane disruptors will result in synthetic antibiotics
that exhibit bactericidal action similar to that of cationic peptides without concomitant
host toxicity, and can thus be used systemically. These synthetic antibiotics will
be designed to penetrate the bacterial cell wall and be stable in vivo.
- The idea is shown schematically below
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