ANTIMICROBIAL PEPTIDES COMPRISING EPSILON LYSINE RESIDUES

The present disclosure relates to a peptide comprising at least five amino acid residues, wherein at least one amino acid residue is modified to an epsilon-lysine, delta-ornithine, gamma-2,4-diaminobutyric acid, beta-2,3-diaminopropionic acid, with the peptide also comprising at least one non-epsilo...

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Hauptverfasser: MAYANDI, Venkatesh, RAJAMANI, Lakshminarayanan, VERMA, Navin Kumar, GOH, Tze Leng Eunice, BEUERMAN, Roger Wilmer
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creator MAYANDI, Venkatesh
RAJAMANI, Lakshminarayanan
VERMA, Navin Kumar
GOH, Tze Leng Eunice
BEUERMAN, Roger Wilmer
description The present disclosure relates to a peptide comprising at least five amino acid residues, wherein at least one amino acid residue is modified to an epsilon-lysine, delta-ornithine, gamma-2,4-diaminobutyric acid, beta-2,3-diaminopropionic acid, with the peptide also comprising at least one non-epsilon lysine, non-delta-ornithine, non-gamma-2,4-diaminobutyric acid or non-beta-2,3-diaminopropionic acid, and wherein the peptide displays a reduced or no cytotoxicity when compared to an equivalent non-modified peptide. In a preferred embodiment, the modifications are to the melittin or mastoparan B peptides, and comprise the substitution of at least one a-lysine residue for an ε-lysine residue, and the modified peptides display antimicrobial activity. The present disclosure is also directed to pharmaceutical compositions, kits, ophthalmic preparations comprising the modified antimicrobial peptides and use of the modified antimicrobial peptides in methods of inhibiting growth of microorganisms, methods of managing microbial colonization, methods of treating proliferative disease, and methods of treating inflammation. The present disclosure also relates to a method of improving the therapeutic index (safety) of an isolated peptide comprising the aforementioned modification.
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In a preferred embodiment, the modifications are to the melittin or mastoparan B peptides, and comprise the substitution of at least one a-lysine residue for an ε-lysine residue, and the modified peptides display antimicrobial activity. The present disclosure is also directed to pharmaceutical compositions, kits, ophthalmic preparations comprising the modified antimicrobial peptides and use of the modified antimicrobial peptides in methods of inhibiting growth of microorganisms, methods of managing microbial colonization, methods of treating proliferative disease, and methods of treating inflammation. 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In a preferred embodiment, the modifications are to the melittin or mastoparan B peptides, and comprise the substitution of at least one a-lysine residue for an ε-lysine residue, and the modified peptides display antimicrobial activity. The present disclosure is also directed to pharmaceutical compositions, kits, ophthalmic preparations comprising the modified antimicrobial peptides and use of the modified antimicrobial peptides in methods of inhibiting growth of microorganisms, methods of managing microbial colonization, methods of treating proliferative disease, and methods of treating inflammation. The present disclosure also relates to a method of improving the therapeutic index (safety) of an isolated peptide comprising the aforementioned modification.</abstract><oa>free_for_read</oa></addata></record>
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subjects CHEMISTRY
HUMAN NECESSITIES
HYGIENE
MEDICAL OR VETERINARY SCIENCE
METALLURGY
ORGANIC CHEMISTRY
PEPTIDES
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS
title ANTIMICROBIAL PEPTIDES COMPRISING EPSILON LYSINE RESIDUES
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