Targeted antimicrobial moieties
Inventors
Eckert, Randal H. • KAPLAN, CHRIS • He, Jian • Yarbrough, Daniel K. • Anderson, Maxwell • SIM, JEE-HYUN
Assignees
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Publication Number
US-9597407-B2
Publication Date
2017-03-21
Expiration Date
Abstract
This invention provides novel targeted antimicrobial compositions. In various embodiments chimeric moieties are provided comprising an antimicrobial peptide attached to a peptide targeting moiety that binds a bacterial strain or species.
Core Innovation
The invention relates to targeted antimicrobial compositions based on chimeric constructs designated as STAMPs (Specifically Targeted Anti-Microbial Peptides). Each chimeric construct includes a microorganism/bacterial-strain targeting peptide attached to an antimicrobial effector moiety to provide targeting and antimicrobial activity. The effector moiety can be an antimicrobial peptide, a photosensitizing agent, a detectable label, or another antimicrobial disruptor/particle.
The construct is formed so the targeting peptide is attached to the effector directly or through a peptide linker, and the disclosed targeting peptide includes the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554). The disclosed platform also includes fusion proteins, optional linker-mediated attachment, and formulation elements such as protecting groups, terminal protection, PEGylation, and non-peptide linkers.
The document further describes antimicrobial action against biofilm and extracellular matrix, including extracellular-matrix-disrupting agents and biofilm enzymes and antimicrobial proteins. It also includes formulations and delivery contexts such as polymeric nanoparticles/microparticles, nanoemulsions/micelles, and liposomes, together with diagnostic concepts using detectable labels or luciferase/ATP readouts and photodynamic antimicrobial methods using light exposure.
Claims Coverage
The provided claim set includes two independent claims. Across them, the inventive features cover a chimeric fusion protein architecture that uses the LATKLKYEKEHKKM (SEQ ID NO:554) targeting peptide attached to an antimicrobial peptide, and a targeted composition that attaches the same targeting peptide to a photosensitizing agent selected from porphyrin, cyanine, and phthalocyanine classes.
Chimeric fusion construct with a specified targeting peptide attached to an antimicrobial peptide
A chimeric construct comprising a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where the targeting peptide is attached to an antimicrobial peptide directly or through a peptide linker, and where the chimeric construct is a fusion protein.
Targeting peptide attached to a photosensitizing agent selected from porphyrin, cyanine, and phthalocyanine classes
A composition comprising a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where the targeting peptide is attached to a photosensitizing agent, and where the photosensitizing agent is selected from the group consisting of a porphyrin, a cyanine, and a phthalocyanine.
The independent claims cover structural chimeric constructs that use the LATKLKYEKEHKKM (SEQ ID NO:554) targeting peptide, either conjugated to an antimicrobial peptide in a fusion protein or conjugated to a photosensitizing agent limited to porphyrin, cyanine, and phthalocyanine classes.
Stated Advantages
Light-dependent, Staphylococcus mutans-selective anti-biofilm activity with limited cytotoxicity.
PEGylation is described as extending serum half-life.
Documented Applications
Selective eradication in mixed cultures using multi-headed STAMP (MH-STAMP M8(KH)-20).
Targeted photodynamic anti-biofilm activity using a targeted STAMP C16-RB (CSP-derived targeting peptide conjugated to rose bengal), described as light-dependent and Staphylococcus mutans-selective with limited cytotoxicity.
Hygiene/oral-care formulation contexts including toothpaste and mouthrinse.
Diagnostic and kit concepts using targeted constructs with permeabilizing dyes or luciferase/ATP readouts.
Targeted antimicrobial compositions providing killing and/or inhibiting growth and/or biofilm disruption for microorganisms, including Gram-positive and Gram-negative bacteria, MRSA, yeasts, and fungi.
Diagnostics using a detectable label attached to a targeting peptide.
Photodynamic antimicrobial methods using targeting peptides conjugated to photosensitizing agents followed by light exposure.
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