Antimicrobial peptides and related methods
Inventors
BOBDE, SHRAVANI • van Hoek, Monique
Assignees
Publication Number
US-12033725-B2
Publication Date
2024-07-09
Expiration Date
2042-08-25
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Abstract
Provided is an engineered antimicrobial peptide. Also provided is a composition comprising an engineered antimicrobial peptide. Provided is a method of treating a subject in need thereof, comprising administering a therapeutically effective amount of a composition comprising an engineered antimicrobial peptide. Also provided is a method of producing an engineered antimicrobial peptide.
Core Innovation
The invention provides engineered antimicrobial peptides (AMPs), specifically comprising certain defined amino acid sequences such as FLLKIVALLKKKLL (SEQ ID NO:1) and others, as well as peptides having at least 70-99% sequence identity to these defined sequences. The invention includes compositions containing one or more of these engineered peptides and methods for producing such peptides using computational approaches based on dataset filtering and positional analysis.
This invention addresses the need for new antimicrobials that can combat multi-drug resistant gram-negative bacterial infections, which present a significant problem due to their outer membrane barrier, resistance mechanisms, and biofilm formation. Traditional antibiotics are becoming less effective, and synthetic AMPs, designed using computational tools to identify motifs and physiochemical properties effective against such bacteria, can provide alternative therapeutic options.
The invention also provides methods for treating subjects by administering therapeutically effective amounts of these engineered peptides, for killing or controlling the growth of microorganisms, and for disinfecting surfaces. Furthermore, it introduces a method of rationally designing new AMPs by creating a dataset of AMPs, selecting candidates by length, calculating the most frequently occurring amino acid at each position, and engineering new sequences accordingly. This approach can target both gram-negative and gram-positive bacteria and even fungi, based on the source data sets used.
Claims Coverage
The patent includes one independent claim covering an engineered antimicrobial peptide with specific sequence characteristics and novelty.
Engineered antimicrobial peptide with defined amino acid sequence and sequence identity
An engineered antimicrobial peptide (AMP) comprising an amino acid sequence selected from the group consisting of: - FLLKIVALLKKKLL (SEQ ID NO:1) or an antimicrobial peptide having at least 90% amino acid sequence identity thereto, - FGKLLKLGKGLGG (SEQ ID NO:2) or at least 90% identity thereto, - FGKLLKLGKGLKG (SEQ ID NO:3) or at least 90% identity thereto, - FLLKLGLGKKKLL (SEQ ID NO:4) or at least 90% identity thereto, - FLIKILKGGKGGK (SEQ ID NO:5) or at least 90% identity thereto, - FIGAIASYLKKFR (SEQ ID NO:6) or at least 90% identity thereto, - GVVDIIKGAGKKFAKGLAGKIANKK (SEQ ID NO:7) or at least 90% identity thereto, - GLMDTVKNAAKNLAGQLLDKIKCKITGC (SEQ ID NO:8) or at least 97% identity thereto. The engineered AMP must not be naturally occurring.
The inventive feature is the provision of non-naturally occurring engineered antimicrobial peptides with defined sequences and high sequence identity to specified novel peptides, distinguishing them from naturally occurring AMPs.
Stated Advantages
Provides novel synthetic peptides with activity against multi-drug resistant gram-negative and gram-positive bacterial infections.
Designed peptides have demonstrated broad-spectrum activity and characteristics that differentiate them from traditional antibiotics.
Offers a computational method to efficiently design and predict functionally active AMPs, reducing time and cost compared to purely in vitro discovery.
Developed peptides show in vitro activity with minimal hemolytic activity, indicating potential for therapeutic use with relatively low toxicity.
Documented Applications
Use in treating infections caused by antibiotic-resistant and susceptible gram-negative and gram-positive bacteria.
Incorporation into compositions for administration to subjects in need of antimicrobial therapy.
Application in disinfecting solutions for decontaminating surfaces of articles.
Use as coatings on medical instruments, catheters, or other substances/materials to impart antimicrobial properties.
Development as topical applicators for treating infected wounds.
Combination with traditional antibiotics, including synergistic or adjunctive use.
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