Peptides and compositions for prevention of cell adhesion and methods of using same
Inventors
Assignees
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Publication Number
US-9732124-B2
Publication Date
2017-08-15
Expiration Date
Abstract
Compositions comprising an isolated peptide, which may for example optionally comprise a sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3) or CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), or any cyclized version thereof, and methods of using same, including for treatment of or prevention of formation of microbial biofilms and against adhesion of a cell to a surface.
Core Innovation
The invention discloses isolated cyclized and non-cyclized anti-adhesive peptides, including cyclized peptides comprising FDYDWY (SEQ ID NO:2) and FNFDWY (SEQ ID NO:5), and larger peptide variants such as SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO:3) and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO:1). The disclosed peptides are used to prevent microbial/biofilm formation and inhibit adhesion of single-cell organisms to surfaces.
The problem addressed is the adhesion of a single cell organism to a surface and the initiation of microbial biofilm formation, which is presented as a key cause of biofilm development on surfaces including medical devices. The invention emphasizes anti-adhesion and biofilm initiation prevention rather than bactericidal action, supporting a mechanism focused on reducing adhesion of microorganisms to a surface.
The disclosed cyclized peptides are applied in the context of surfaces of medical devices, including artificial blood vessels, catheters, artificial hearts, artificial kidneys, orthopedic pins, prosthetic joints, plates, urinary devices, ventricular or arterio-venous shunts, prostheses, breast implants, penile prostheses, vascular grafting prostheses, aneurysm repair devices, mechanical heart valves, artificial joints, artificial larynxes, otological implants, anastomotic devices, vascular catheter ports, vascular stents, clamps, embolic devices, wound drain tubes, ocular lenses, dental implants, hydrocephalus shunts, pacemakers and implantable defibrillators, needleless connectors, and voice prostheses.
Claims Coverage
The independent claim covers a method of inhibiting adhesion of a single cell organism to a medical-device surface by contacting the organism with a composition comprising a cyclized peptide (up to 35 amino acids) containing a sequence selected from FDYDWY (SEQ ID NO:2) and FNFDWY (SEQ ID NO:5), or combinations thereof. The independent claim is supplemented by dependent claims that refine peptide sequence variants and/or presentation on the device surface, and that narrow to particular devices and constraints on peptide length.
Cyclized peptide up to 35 amino acids for inhibiting adhesion
A method of inhibiting adhesion of a single cell organism to a surface by contacting the organism with a composition comprising a cyclized peptide consisting of a length of up to 35 amino acids and comprising a sequence selected from FDYDWY (SEQ ID NO:2) and FNFDWY (SEQ ID NO:5) or combinations thereof.
Medical-device surface for adhesion inhibition
The method wherein the surface is in a medical device selected from the group consisting of artificial blood vessels, catheters and other devices for the removal or delivery of fluids to patients, artificial hearts, artificial kidneys, orthopedic pins, prosthetic joints, plates, urinary devices, ventricular or arterio-venous shunts, prostheses, breast implants, penile prostheses, vascular grafting prostheses, aneurysm repair devices, mechanical heart valves, artificial joints, artificial larynxes, otological implants, anastomotic devices, vascular catheter ports, vascular stents, clamps, embolic devices, wound drain tubes, ocular lenses, dental implants, hydrocephalus shunts, pacemakers and implantable defibrillators, needleless connectors, and voice prostheses.
Covalent attachment of the composition to the surface
The method wherein the composition is covalently attached to the surface.
Peptide sequence FNFDWY length constraint
The method wherein the peptide comprises the sequence FNFDWY (SEQ ID NO:2) and is up to 26 amino acids long.
Cyclizing using a linker attached to both C and N termini
The method wherein the cyclizing of the peptide is performed using a linker attached to both the C and N termini.
Coating the composition onto the surface of the device
The method wherein the composition is coated onto the surface of the device.
Ocular lens surface
The method wherein the device is an ocular lens.
Across the independent claim and its refinements, the core coverage is directed to inhibiting adhesion of a single cell organism to a surface of a medical device by contacting the organism with a cyclized peptide (up to 35 amino acids) containing FDYDWY (SEQ ID NO:2) and/or FNFDWY (SEQ ID NO:5), with dependent claims further specifying covalent attachment, particular sequence/length constraints, cyclization via a linker at both termini, coating presentation on the device surface, and narrowing to an ocular lens device.
Stated Advantages
Inhibits adhesion of a single cell organism to a surface.
Prevents microbial/biofilm formation by targeting adhesion/biofilm initiation rather than bactericidal action.
Provides anti-adhesive activity for use on a broad range of medical device surfaces.
Documented Applications
Anti-adhesion and prevention of microbial/biofilm formation on surfaces of medical devices including catheters, mechanical heart valves, implants, and ocular lenses.
Use as an anti-fouling composition to inhibit adhesion of single-cell organisms to surfaces.
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