Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis
There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic a...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
22 February 2016
|
| In: |
Antimicrobial agents and chemotherapy
Year: 2016, Jahrgang: 60, Heft: 5, Pages: 2813-2821 |
| ISSN: | 1098-6596 |
| DOI: | 10.1128/AAC.00157-16 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1128/AAC.00157-16 Verlag, lizenzpflichtig, Volltext: https://aac.asm.org/content/60/5/2813 
|
| Verfasserangaben: | Éanna Forde, André Schütte, Emer Reeves, Catherine Greene, Hilary Humphreys, Marcus Mall, Deirdre Fitzgerald-Hughes, Marc Devocelle |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1698605188 | ||
| 003 | DE-627 | ||
| 005 | 20220818092636.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200520s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1128/AAC.00157-16 |2 doi | |
| 035 | |a (DE-627)1698605188 | ||
| 035 | |a (DE-599)KXP1698605188 | ||
| 035 | |a (OCoLC)1341325969 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Forde, Éanna |e VerfasserIn |0 (DE-588)1208739867 |0 (DE-627)1695562542 |4 aut | |
| 245 | 1 | 0 | |a Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis |c Éanna Forde, André Schütte, Emer Reeves, Catherine Greene, Hilary Humphreys, Marcus Mall, Deirdre Fitzgerald-Hughes, Marc Devocelle |
| 264 | 1 | |c 22 February 2016 | |
| 300 | |a 9 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 20.05.2020 | ||
| 520 | |a There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE). However, cytotoxicity remained an issue. Here, we describe the further optimization of the AMP prodrug (pro-AMP) model for CF to produce pro-WMR, a peptide with greatly reduced cytotoxicity (50% inhibitory concentration against CFBE41o- cells, >300 μM) compared to that of the previous group of pro-AMPs. The bactericidal activity of pro-WMR was increased in NE-rich bronchoalveolar lavage (BAL) fluid from CF patients (range, 8.4% ± 6.9% alone to 91.5% ± 5.8% with BAL fluid; P = 0.0004), an activity differential greater than that of previous pro-AMPs. In a murine model of lung delivery, the pro-AMP modification reduced host toxicity, with pro-WMR being less toxic than the active peptide. Previously, host toxicity issues have hampered the clinical application of AMPs. However, the development of application-specific AMPs with modifications that minimize toxicity similar to those described here can significantly advance their potential use in patients. The combination of this prodrug strategy with a highly active AMP has the potential to produce new therapeutics for the challenging conditions of the CF patient lung. | ||
| 700 | 1 | |a Schütte, André |d 1980- |e VerfasserIn |0 (DE-588)140311718 |0 (DE-627)617693897 |0 (DE-576)31637220X |4 aut | |
| 700 | 1 | |a Reeves, Emer |e VerfasserIn |4 aut | |
| 700 | 1 | |a Greene, Catherine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Humphreys, Hilary |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mall, Marcus A. |d 1975- |e VerfasserIn |0 (DE-588)115507795 |0 (DE-627)691370532 |0 (DE-576)28992152X |4 aut | |
| 700 | 1 | |a Fitzgerald-Hughes, Deirdre |e VerfasserIn |4 aut | |
| 700 | 1 | |a Devocelle, Marc |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Antimicrobial agents and chemotherapy |d Washington, DC : Soc., 1972 |g 60(2016), 5, Seite 2813-2821 |h Online-Ressource |w (DE-627)306316919 |w (DE-600)1496156-8 |w (DE-576)09718859X |x 1098-6596 |7 nnas |a Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis |
| 773 | 1 | 8 | |g volume:60 |g year:2016 |g number:5 |g pages:2813-2821 |g extent:9 |a Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis |
| 856 | 4 | 0 | |u https://doi.org/10.1128/AAC.00157-16 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://aac.asm.org/content/60/5/2813 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200520 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 115507795 |a Mall, Marcus A. |m 115507795:Mall, Marcus A. |d 910000 |d 910500 |e 910000PM115507795 |e 910500PM115507795 |k 0/910000/ |k 1/910000/910500/ |p 6 | ||
| 998 | |g 140311718 |a Schütte, André |m 140311718:Schütte, André |d 910000 |d 910500 |e 910000PS140311718 |e 910500PS140311718 |k 0/910000/ |k 1/910000/910500/ |p 2 | ||
| 999 | |a KXP-PPN1698605188 |e 366876302X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedKey":"2016","dateIssuedDisp":"22 February 2016"}],"id":{"doi":["10.1128/AAC.00157-16"],"eki":["1698605188"]},"name":{"displayForm":["Éanna Forde, André Schütte, Emer Reeves, Catherine Greene, Hilary Humphreys, Marcus Mall, Deirdre Fitzgerald-Hughes, Marc Devocelle"]},"physDesc":[{"extent":"9 S."}],"relHost":[{"note":["Gesehen am 09.06.21"],"disp":"Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosisAntimicrobial agents and chemotherapy","type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"306316919","corporate":[{"roleDisplay":"Herausgebendes Organ","display":"American Society for Microbiology","role":"isb"}],"language":["eng"],"pubHistory":["1.1972 -"],"titleAlt":[{"title":"AAC"}],"part":{"extent":"9","volume":"60","text":"60(2016), 5, Seite 2813-2821","issue":"5","pages":"2813-2821","year":"2016"},"title":[{"title_sort":"Antimicrobial agents and chemotherapy","title":"Antimicrobial agents and chemotherapy","subtitle":"AAC"}],"physDesc":[{"extent":"Online-Ressource"}],"name":{"displayForm":["publ. by the American Society for Microbiology"]},"origin":[{"dateIssuedKey":"1972","publisher":"Soc.","dateIssuedDisp":"1972-","publisherPlace":"Washington, DC"}],"id":{"issn":["1098-6596"],"zdb":["1496156-8"],"eki":["306316919"]}}],"title":[{"title_sort":"Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis","title":"Differential in vitro and in vivo toxicities of antimicrobial peptide prodrugs for potential use in cystic fibrosis"}],"person":[{"given":"Éanna","family":"Forde","role":"aut","roleDisplay":"VerfasserIn","display":"Forde, Éanna"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Schütte, André","given":"André","family":"Schütte"},{"given":"Emer","family":"Reeves","role":"aut","roleDisplay":"VerfasserIn","display":"Reeves, Emer"},{"family":"Greene","given":"Catherine","roleDisplay":"VerfasserIn","display":"Greene, Catherine","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Humphreys, Hilary","given":"Hilary","family":"Humphreys"},{"roleDisplay":"VerfasserIn","display":"Mall, Marcus A.","role":"aut","family":"Mall","given":"Marcus A."},{"roleDisplay":"VerfasserIn","display":"Fitzgerald-Hughes, Deirdre","role":"aut","family":"Fitzgerald-Hughes","given":"Deirdre"},{"given":"Marc","family":"Devocelle","role":"aut","display":"Devocelle, Marc","roleDisplay":"VerfasserIn"}],"note":["Gesehen am 20.05.2020"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"recId":"1698605188","language":["eng"]} | ||
| SRT | |a FORDEEANNADIFFERENTI2220 | ||