scholarly journals Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

2011 ◽  
Vol 55 (6) ◽  
pp. 2880-2890 ◽  
Author(s):  
Gopinath Kasetty ◽  
Praveen Papareddy ◽  
Martina Kalle ◽  
Victoria Rydengård ◽  
Matthias Mörgelin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Host Defense ◽  
Host Defense Peptides ◽  
Content Type ◽  
Peptide Epitopes ◽  
Structure Activity ◽  
Human Thrombin ◽  
Defense Peptides ◽  
Anti Inflammatory

ABSTRACTPeptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteriaEscherichia coliandPseudomonas aeruginosa, the Gram-positive bacteriumStaphylococcus aureus, and the fungusCandida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock andP. aeruginosasepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

Structure−activity Relationships among Random Nylon-3 Copolymers That Mimic Antibacterial Host-Defense Peptides

2009 ◽  
Vol 131 (28) ◽  
pp. 9735-9745 ◽  
Author(s):  
Brendan P. Mowery ◽  
Alexandra H. Lindner ◽  
Bernard Weisblum ◽  
Shannon S. Stahl ◽  
Samuel H. Gellman
Keyword(s):  
Host Defense ◽  
Host Defense Peptides ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Defense Peptides ◽  
Antibacterial Host Defense

scholarly journals Differential Expression of Caprine β-Defensins in Digestive and Respiratory Tissues

1999 ◽  
Vol 67 (11) ◽  
pp. 6221-6224 ◽  
Author(s):  
Chengquan Zhao ◽  
Tung Nguyen ◽  
Lide Liu ◽  
Olga Shamova ◽  
Kim Brogden ◽  
...  
Keyword(s):  
Amino Acids ◽  
Respiratory Tract ◽  
Differential Expression ◽  
Host Defense ◽  
Specific Expression ◽  
Host Defense Peptides ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Defense Peptides

ABSTRACT We identified two novel β-defensin precursors, preproGBD-1 and preproGBD-2, in the tissues of a goat. Although the precursors were identical in 96.8% of their bases and 88.2% (60 of 68) of their amino acids, preproGBD-1 was expressed principally in the tongue and respiratory tract, whereas preproGBD-2 expression predominated throughout the intestine. These findings exemplify the phenomenon of tissue-specific expression in a family of host defense peptides that arose before the avian and mammalian lineages diverged.

scholarly journals How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

2019 ◽  
Vol 20 (21) ◽  
pp. 5289 ◽  
Author(s):  
Adenrele Oludiran ◽  
David S. Courson ◽  
Malia D. Stuart ◽  
Anwar R. Radwan ◽  
John C. Poutsma ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Bacterial Species ◽  
Membrane Curvature ◽  
Lessons Learned ◽  
Health Concern ◽  
Copper Binding ◽  
Bacterial Killing ◽  
Host Defense Peptides ◽  
Defense Peptides

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue.

Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity

Biochimie ◽  
2010 ◽  
Vol 92 (9) ◽  
pp. 1236-1241 ◽  
Author(s):  
Daisuke Takahashi ◽  
Sanjeev K. Shukla ◽  
Om Prakash ◽  
Guolong Zhang
Keyword(s):  
Antimicrobial Activity ◽  
Host Defense ◽  
Target Cell ◽  
Structural Determinants ◽  
Host Defense Peptides ◽  
Cell Selectivity ◽  
Defense Peptides

scholarly journals Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides

2016 ◽  
Vol 17 (7) ◽  
pp. 1023 ◽  
Author(s):  
Hao Li ◽  
Nuttapat Anuwongcharoen ◽  
Aijaz Malik ◽  
Virapong Prachayasittikul ◽  
Jarl Wikberg ◽  
...  
Keyword(s):  
Amino Acids ◽  
Host Defense ◽  
Host Defense Peptides ◽  
Defense Peptides

scholarly journals Proteolysis of Human Thrombin Generates Novel Host Defense Peptides

2010 ◽  
Vol 6 (4) ◽  
pp. e1000857 ◽  
Author(s):  
Praveen Papareddy ◽  
Victoria Rydengård ◽  
Mukesh Pasupuleti ◽  
Björn Walse ◽  
Matthias Mörgelin ◽  
...  
Keyword(s):  
Host Defense ◽  
Host Defense Peptides ◽  
Human Thrombin ◽  
Novel Host ◽  
Defense Peptides

scholarly journals Efficacy of Antimicrobial Peptoids against Mycobacterium tuberculosis

2011 ◽  
Vol 55 (6) ◽  
pp. 3058-3062 ◽  
Author(s):  
Rinki Kapoor ◽  
Patrick R. Eimerman ◽  
Jonathan W. Hardy ◽  
Jeffrey D. Cirillo ◽  
Christopher H. Contag ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cause Of Death ◽  
Host Defense ◽  
Natural Host ◽  
Antituberculosis Drug ◽  
Host Defense Peptides ◽  
Content Type ◽  
Defense Peptides

ABSTRACTTuberculosis is a leading cause of death worldwide. Resistance ofMycobacteriumto antibiotics can make treatments less effective in some cases. We tested selected oligopeptoids—previously reported as mimics of natural host defense peptides—for activity againstMycobacterium tuberculosisand assessed their cytotoxicity. A tetrameric, alkylated, cationic peptoid (1-C134mer) was most potent againstM. tuberculosisand least cytotoxic, whereas an unalkylated analogue, peptoid 14mer, was inactive. Peptoid 1-C134merthus merits further study as a potential antituberculosis drug.

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