title: Using Disease-Associated Enzymes to Activate Antimicrobial Peptide Prodrugs.
abstract: Prodrugs of antimicrobial peptides can be generated by modifying their sequences at their N-termini with a linker and a negatively charged promoiety. These modifications can be selectively reversed by a disease-associated enzyme, thereby confining the activity of the peptide to pathologically affected body parts. A general method for the generation of prodrug candidates, based on a linker constituting the substrate of a disease-associated protease and an oligo-glutamic acid promoiety, as well as a protocol to validate the activation of the prodrug, are described herein.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen's Green, Dublin 2, Ireland.|Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Dublin, Ireland.
authors.forename: Éanna B
authors.initials: ÉB
authors.lastname: Forde
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen's Green, Dublin 2, Ireland.
authors.forename: Graeme
authors.initials: G
authors.lastname: Kelly
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen's Green, Dublin 2, Ireland.|Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Dublin, Ireland.
authors.forename: Hisham
authors.initials: H
authors.lastname: Makki
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen's Green, Dublin 2, Ireland.|Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Dublin, Ireland.
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Al-Sharshahi
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Fitzgerald-Hughes
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen's Green, Dublin 2, Ireland. mdevocelle@rcsi.ie.
authors.forename: Marc
authors.initials: M
authors.lastname: Devocelle
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D011355:Prodrugs; D010447:Peptide Hydrolases
keywords: Active parent AMP; Disease-associated protease; Oligo-glutamic acid promoiety; Prodrug activation