Antimicrobial peptides
Inventors
He, Jian • Eckert, Randal H. • Qi, Fengxia • Anderson, Maxwell H. • Shi, Wenyuan
Assignees
University of California San Diego UCSD • C3J Therapeutics Inc
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Publication Number
US-8609608-B2
Publication Date
2013-12-17
Expiration Date
Abstract
This invention provides novel antimicrobial peptides that are effective to inhibit growth and/or proliferation of various gram positive bacteria. In particular, the peptides are effective against Streptococcus mutans a common oral pathogen and the causative agent of dental caries.
Core Innovation
The invention relates to antimicrobial peptide scaffolds designed for activity against Gram-positive bacteria, including Streptococcus mutans associated with dental caries. The peptides are defined by selected amino acid sequences of up to about 25 amino acids and are stated to have antimicrobial activity against S. mutans at an acidic pH.
The disclosed peptides include His-rich amphipathic helical architectures based on motif and formula frameworks with variable hydrophobic (H) and charged or neutral (C) residues. The core design specifies antimicrobial peptide sequences HHFFHHFHHFFHHF (SEQ ID NO:109) (AA-1), FHFFHHFFHFFHHF (SEQ ID NO:110) (AA-2), KLLKGAT FHFFHHFFHFFHHF (SEQ ID NO:111) (AA-3), KLLKFHFFHHFFHFFHHF (SEQ ID NO:112) (AA-4), and FHFFHHFFHFFHHFKLLK (SEQ ID NO:113) (AA-5), and the acid-activated activity is associated with His-rich content described as active at acidic pH.
In addition to the peptide sequence framework, the disclosure addresses related embodiments in which antimicrobial peptides are provided as fusion or conjoined AMP peptides and highlights that antibacterial effects can depend on linker presence and composition. The document also describes peptide modification embodiments, including compound AMPs formed by conjugation or fusion and peptide modifications such as D-amino acids, beta/retro/inverse/retro-inverso, protecting groups, and pegylation.
Claims Coverage
The provided claim coverage centers on one independent claim and dependent refinements. It covers five specific antimicrobial peptide amino-acid sequences, with additional dependent features relating to protecting groups.
Acidic-pH antimicrobial activity against S. mutans
An antimicrobial peptide of up to about 25 amino acids comprising an amino acid sequence selected from HHFFHHFHHFFHHF (SEQ ID NO:109) (AA-1), FHFFHHFFHFFHHF (SEQ ID NO:110) (AA-2), KLLKGAT FHFFHHFFHFFHHF (SEQ ID NO:111) (AA-3), KLLKFHFFHHFFHFFHHF (SEQ ID NO:112) (AA-4), and FHFFHHFFHFFHHFKLLK (SEQ ID NO:113) (AA-5), wherein the peptide has antimicrobial activity against S. mutans at an acidic pH.
Sequence variant restriction to listed peptide sequences
The peptide is limited to the specific listed amino-acid sequence variants corresponding to AA-1, AA-2, AA-3, AA-4, and AA-5 as recited in the claim set.
Protecting groups selected from an enumerated set
The antimicrobial peptide further includes one or more protecting groups selected from a listed set of chemical protecting group moieties, as refined in dependent claims.
Coverage is directed to antimicrobial peptides of up to about 25 amino acids restricted to the stated sequence variants and characterized by antimicrobial activity against S. mutans at acidic pH, with dependent refinements that add specified protecting-group chemistry.
Stated Advantages
Antimicrobial activity against S. mutans at an acidic pH.
Documented Applications
Pharmaceutical and oral healthcare products, including toothpaste, mouthwash, dental floss, swabs, and related product embodiments, as well as kits.
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