Boosting antimicrobial peptides by hydrophobic oligopeptide end tags.

Schmidtchen, ArturLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

A novel approach for boosting antimicrobial peptides through end tagging with hydrophobic oligopeptide stretches is demonstrated. Focusing on two peptides derived from kininogen, GKHKNKGKKNGKHNGWK (GKH17) and HKHGHGHGKHKNKGKKN (HKH17), tagging resulted in enhanced killing of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungal Candida albicans. Microbicidal potency increased with tag length, also in plasma, and was larger for Trp and Phe stretches than for aliphatic ones. The enhanced microbicidal effects correlated to a higher degree of bacterial wall rupture. Analogously, tagging promoted peptide binding to model phospholipid membranes and liposome rupture, particularly for anionic and cholesterol-void membranes. Tagged peptides displayed low toxicity, particularly in the presence of serum, and resisted degradation by human leukocyte elastase and by staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo and in vivo in porcine S. aureus skin infection models. The generality of end tagging for facile boosting of antimicrobial peptides without the need for post-synthesis modification was also demonstrated.

Pasupuleti, MukeshLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-mhp (author)
Mörgelin, MatthiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-mmn (author)
Davoudi, MinaLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infektionsmedicin,Institutionen för kliniska vetenskaper, Lund,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Infection Medicine (BMC),Department of Clinical Sciences, Lund(Swepub:lu)derm-mda (author)
Alenfall, Jan (author)
Chalupka, AnnaLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-aac (author)
Malmsten, MartinUppsala University,Uppsala universitet,Institutionen för farmaci(Swepub:lu)ma1014ma (author)
Dermatologi och venereologi, LundSektion III (creator_code:org_t)

By the author/editor: Schmidtchen, Art ...; Pasupuleti, Muke ...; Mörgelin, Matthi ...; Davoudi, Mina; Alenfall, Jan; Chalupka, Anna; show more...; Malmsten, Martin; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

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