Antimicrobial and anticancer peptides and conjugates and compositions, methods, articles and kits relating thereto
Inventors
Bishop, Barney • Sahoo, Saswata K. • Davis, Justin
Assignees
George Mason University • George Mason Research Foundation Inc
Publication Number
US-11447533-B2
Publication Date
2022-09-20
Expiration Date
2039-12-11
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Abstract
Peptides and conjugates are described herein, including peptides having antimicrobial and/or anticancer properties, as are compositions, articles, and kits comprising such peptides and conjugates, and methods for using the peptides and conjugates.
Core Innovation
The invention provides novel peptides and conjugates, including peptides defined by specific amino acid sequences, that demonstrate antimicrobial and/or anticancer properties. These peptides can be optionally modified through substitutions, insertions, additions, or deletions to optimize or alter their activity. The invention also includes polynucleotides encoding these peptides, as well as compositions, articles, and kits that incorporate them. Methods for the use of these peptides and their conjugates in therapeutic, prophylactic, and diagnostic applications are disclosed.
Current challenges in the delivery of antimicrobial and anticancer agents include toxicity to normal cells and lack of specificity for targeting harmful organisms or cancerous cells. Existing polylysine-based constructs do not provide sufficient specificity and are not optimal for systemic administration. There remains a need for agents and strategies that can effectively target and treat microbial infections and cancers with improved specificity and efficacy, while reducing undesired effects on healthy cells.
The peptides described in this invention are designed to address these issues by providing sequences with selective antimicrobial and anticancer activities, and the capacity to bind to microbial components such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA). The peptides and their conjugates can be tailored for enhanced targeting, delivery of therapeutic or diagnostic agents to specific cells, and for use in diverse compositions for medical, environmental, and diagnostic purposes. This includes methods for treating infections, cancers, promoting wound healing, neutralizing endotoxins, and detecting or isolating pathogens or tumor cells.
Claims Coverage
The patent contains five independent claims, each addressing a distinct inventive feature relating to antimicrobial and anticancer peptides.
Peptide with specific amino acid sequences
A peptide comprising the amino acid sequence set forth in SEQ ID NO: 7, 8, 9, 11, 12, 13, 14, or 15.
Peptide with linked segment
The peptide further comprises a linked segment having a linked segment amino acid sequence of SEQ ID NO: 17 or 20.
Polynucleotide encoding the peptide
A polynucleotide encoding the peptide comprising the sequence set forth in SEQ ID NO: 7, 8, 9, 11, 12, 13, 14, or 15.
Composition containing the peptide or encoding polynucleotide
A composition comprising the peptide (as claimed above) or a polynucleotide encoding the peptide.
Conjugate of peptide with delivery agent
A conjugate comprising the peptide (SEQ ID NO: 7, 8, 9, 11, 12, 13, 14, or 15) conjugated to an agent, with the peptide connected to the agent directly or through a linker segment, where the agent is connected through a stable or cleavable bond, and the conjugate facilitates delivery of the agent to a microbe or a cancer cell or a tumor cell.
In summary, the claims cover peptide sequences with defined structure, peptides with linked segments, corresponding encoding polynucleotides, compositions containing these peptides or polynucleotides, and peptide-based conjugates for targeted delivery to microbes or cancer cells.
Stated Advantages
The peptides exhibit selective antimicrobial and/or anticancer activity, with improved specificity for microbial organisms and cancerous cells while limiting toxicity toward normal cells.
The invention provides therapeutic agents and methods that are effective against drug-resistant and multidrug-resistant pathogens.
Peptides and their conjugates can neutralize or bind endotoxins such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), thereby reducing toxicity and the risk of endotoxemia.
Peptide conjugates allow for targeted delivery of therapeutic or diagnostic agents to microbes or tumor cells, facilitating effective treatment or detection.
Formulations and coatings using the peptides offer potential for inhibiting biofilm growth on medical devices and other surfaces.
Some peptides and conjugates promote wound healing, including applications for wounds that are infected or uninfected.
Documented Applications
Treatment of infection by microbial organisms including bacteria, viruses, fungi, and protozoa in humans, companion animals, or livestock.
Reduction, prevention, or inhibition of growth of microbial organisms or biofilms on surfaces such as environmental surfaces, medical devices, prosthetics, or implants.
Promotion of wound healing in subjects, including both infected and uninfected wounds.
Treatment or prevention of endotoxemia in a subject by administering peptides that bind to endotoxins like LPS or LTA.
Determination and diagnosis of the presence of LPS or LTA in biological samples, and diagnosing related disorders.
Treatment of compositions (such as blood, plasma, serum, bone marrow, or cell culture reagents) by reducing or eliminating LPS or LTA through peptide binding.
Treatment or prevention of cancer in subjects by administering peptides or compositions comprising such peptides.
Targeted delivery of therapeutic or diagnostic agents to microbes, cancer cells, or tumor cells using peptide conjugates.
Isolation and detection of bacteria or tumor cells from samples using peptides in free form, conjugated to an agent, or bound to a solid phase.
Coating articles or invasive devices (e.g., surgical tools, implants, catheters, staples, sutures, tubing) with the peptides for antimicrobial or anti-endotoxin activity.
Use in hygiene products such as mouthwash and body wash, and in wound dressings.
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