Probing structure–activity relationships in bactericidal peptide βpep-25

2008 ◽  
Vol 414 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Ruud P. M. Dings ◽  
Judith R. Haseman ◽  
Kevin H. Mayo

Cationic peptides, known to disrupt bacterial membranes, are being developed as promising agents for therapeutic intervention against infectious disease. In the present study, we investigate structure–activity relationships in the bacterial membrane disruptor βpep-25, a peptide 33-mer. For insight into which amino acid residues are functionally important, we synthesized alanine-scanning variants of βpep-25 and assessed their ability to kill bacteria (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) and to neutralize LPS (lipopolysaccharide). Activity profiles were found to vary with the bacterial strain examined. Specific cationic and smaller hydrophobic alkyl residues were crucial to optimal bactericidal activity against the Gram-negative bacteria, whereas larger hydrophobic and cationic residues mediated optimal activity against Gram-positive Staph. aureus. Lysine-substituted norleucine (n-butyl group) variants demonstrated that both charge and alkyl chain length mediate optimal activity. In terms of LPS neutralization, activity profiles were essentially the same against four species of LPS (E. coli 055 and 0111, Salmonella enterica serotype Typhimurium and Klebsiella pneumoniae), and different for two others (Ps. aeruginosa and Serratia marcescens), with specific hydrophobic, cationic and, surprisingly, anionic residues being functionally important. Furthermore, disulfide-bridged analogues demonstrated that an anti parallel β-sheet structure is the bioactive conformation of βpep-25 in terms of its bactericidal, but not LPS endotoxin neutralizing, activity. Moreover, βpep-25 variants, like the parent peptide, do not lyse eukaryotic cells. This research contributes to the development and design of novel antibiotics.

2011 ◽  
Vol 76 (12) ◽  
pp. 1597-1606 ◽  
Author(s):  
Nemanja Trisovic ◽  
Bojan Bozic ◽  
Ana Obradovic ◽  
Olgica Stefanovic ◽  
Snezana Markovic ◽  
...  

A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 ?M, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.


2017 ◽  
Vol 109 ◽  
pp. 975-983 ◽  
Author(s):  
Zi-Miao Weng ◽  
Ping Wang ◽  
Guang-Bo Ge ◽  
Zi-Ru Dai ◽  
Da-Chang Wu ◽  
...  

2017 ◽  
Vol 41 (11) ◽  
pp. 645-649 ◽  
Author(s):  
Long-Fei Mao ◽  
Gui-Qing Xu ◽  
Bin Sun ◽  
Yu-Qin Jiang ◽  
Wen-Pei Dong ◽  
...  

A series of novel 1,2,3-triazole derivatives incorporating 3′-deoxythymidine were designed, synthesised and characterised. Antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated for all of the synthesised compounds and compared against standard antibiotic drugs, streptomycin sulfate and doxycycline, as controls. Some compounds showed potential antibacterial activity towards E. coli, and the best minimum inhibitory concentration was 0.14 mM. Preliminary structure-activity relationships and computational simulations were also studied.


2005 ◽  
Vol 3 (5) ◽  
pp. 886-900 ◽  
Author(s):  
Jörgen Ohlsson ◽  
Andreas Larsson ◽  
Sauli Haataja ◽  
Jenny Alajääski ◽  
Peter Stenlund ◽  
...  

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 343
Author(s):  
Agata Ładniak ◽  
Małgorzata Jurak ◽  
Marta Palusińska-Szysz ◽  
Agnieszka Ewa Wiącek

The aim of the study was to determine the bactericidal properties of popular medical, pharmaceutical, and cosmetic ingredients, namely chitosan (Ch), hyaluronic acid (HA), and titanium dioxide (TiO2). The characteristics presented in this paper are based on the Langmuir monolayer studies of the model biological membranes formed on subphases with these compounds or their mixtures. To prepare the Langmuir film, 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) phospholipid, which is the component of most bacterial membranes, as well as biological material-lipids isolated from bacteria Escherichia coli and Staphylococcus aureus were used. The analysis of the surface pressure-mean molecular area (π-A) isotherms, compression modulus as a function of surface pressure, CS−1 = f(π), relative surface pressure as a function of time, π/π0 = f(t), hysteresis loops, as well as structure visualized using a Brewster angle microscope (BAM) shows clearly that Ch, HA, and TiO2 have antibacterial properties. Ch and TiO2 mostly affect S. aureus monolayer structure during compression. They can enhance the permeability of biological membranes leading to the bacteria cell death. In turn, HA has a greater impact on the thickness of E. coli film.


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