Peptides and compositions for prevention of cell adhesion and methods of using same
Inventors
Zlotkin, Amir • Kestenboim, Hen
Assignees
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Publication Number
US-9777050-B2
Publication Date
2017-10-03
Expiration Date
Abstract
Compositions comprising an isolated peptide, which may for example optionally comprise a sequence selected from the group consisting of YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), YDWHLY (SEQ ID NO: 7), and WDYNLY (SEQ ID NO: 8), extracted from organisms such as aquatic organisms and moss or any other sequence described herein, 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 relates to isolated natural anti-adhesive peptides defined by conserved short sequence motifs. The peptides are exemplified by sequences including YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), WDYNLY (SEQ ID NO: 8), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), and YDWHLY (SEQ ID NO: 7). The peptides are described as anti-adhesive peptides that prevent cell adhesion.
The disclosed peptides are used to prevent early-stage microbial biofilm formation without killing or inhibiting bacterial growth. The described activity is broad-spectrum across multiple bacterial species, and synthetic peptide testing is described as showing no bactericidal or bacteriostatic effect while reducing biofilm formation.
The invention further includes cyclic peptide embodiments derived from the sequence motifs, where the peptide is cyclized by a covalent bond. Optional cyclization via an amide bond or a disulfide bridge is described, as well as optional emulsifying/hydrophobic arms to support anti-fouling surface absorption. Delivery is envisioned as compositions/pharmaceuticals and as surface/device coatings for anti-fouling applications.
Claims Coverage
The independent claim covers cyclic peptides comprising specified sequence motifs with a covalent cyclization linkage and a total length constraint. The claim family further narrows peptide length thresholds and specifies the covalent linkage type and particular sequence embodiments.
Specified cyclic peptide sequences with covalent cyclization and maximum length
A cyclic peptide comprising one of the sequences YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), WDYNLY (SEQ ID NO: 8), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), and YDWHLY (SEQ ID NO: 7), wherein the peptide is cyclized by a covalent bond, and wherein the total length of the peptide is 50 amino acids or less.
Cyclic peptide length narrowed to 40 amino acids or less
The peptide of claim 1 has a total length of 40 amino acids or less.
Cyclic peptide length narrowed to 30 amino acids or less
The claim covers a peptide having a total length of 30 amino acids or less.
Cyclic peptide including YDYNWY sequence with maximum length
A cyclic peptide includes the sequence YDYNWY (SEQ ID NO: 1) and has a total length of 30 amino acids or less.
Covalent cyclization via amide bond or disulfide bridge
The claimed peptide is cyclized via either an amide bond or a disulfide bridge.
Overall, the claim coverage centers on cyclic peptides made from specific conserved sequence motifs that are cyclized by a covalent bond, with peptide length limited to 50 amino acids or less and further narrowed to 40 or 30 amino acids or less in dependent coverage. Additional dependent coverage specifies particular sequence embodiments, including YDYNWY, and restricts the cyclization chemistry to an amide bond or a disulfide bridge.
Stated Advantages
Prevention of cell adhesion.
Prevention of early-stage microbial biofilm formation.
No bactericidal effect and no bacteriostatic effect, while reducing biofilm formation.
Broad-spectrum activity across multiple bacterial species.
Documented Applications
Anti-fouling coatings for marine applications, including marine anti-fouling use cases and examples involving reverse osmosis biofouling.
Coatings for medical devices.
Anti-fouling for water purification reverse osmosis (RO) systems.
Compositions/pharmaceutical delivery for preventing adhesion and early-stage microbial biofilm formation.
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