A Novel Amphipathic Linear Peptide with Both Insect Toxicity and Antimicrobial Activity from the Venom of the ScorpionIsometrus maculatus

2010 ◽  
Vol 74 (2) ◽  
pp. 364-369 ◽  
Author(s):  
Masahiro MIYASHITA ◽  
Atsushi SAKAI ◽  
Nobuto MATSUSHITA ◽  
Yosuke HANAI ◽  
Yoshiaki NAKAGAWA ◽  
...  
2021 ◽  
Vol 9 (6) ◽  
pp. 1249
Author(s):  
Johannes Koehbach ◽  
Jurnorain Gani ◽  
Kai Hilpert ◽  
David J Craik

According to the World Health Organization (WHO) the development of resistance against antibiotics by microbes is one of the most pressing health concerns. The situation will intensify since only a few pharmacological companies are currently developing novel antimicrobial compounds. Discovery and development of novel antimicrobial compounds with new modes of action are urgently needed. Antimicrobial peptides (AMPs) are known to be able to kill multidrug-resistant bacteria and, therefore, of interest to be developed into antimicrobial drugs. Proteolytic stability and toxicities of these peptides are challenges to overcome, and one strategy frequently used to address stability is cyclization. Here we introduced a disulfide-bond to cyclize a potent and nontoxic 9mer peptide and, in addition, as a proof-of-concept study, grafted this peptide into loop 6 of the cyclotide MCoTI-II. This is the first time an antimicrobial peptide has been successfully grafted onto the cyclotide scaffold. The disulfide-cyclized and grafted cyclotide showed moderate activity in broth and strong activity in 1/5 broth against clinically relevant resistant pathogens. The linear peptide showed superior activity in both conditions. The half-life time in 100% human serum was determined, for the linear peptide, to be 13 min, for the simple disulfide-cyclized peptide, 9 min, and, for the grafted cyclotide 7 h 15 min. The addition of 10% human serum led to a loss of antimicrobial activity for the different organisms, ranging from 1 to >8-fold for the cyclotide. For the disulfide-cyclized version and the linear version, activity also dropped to different degrees, 2 to 18-fold, and 1 to 30-fold respectively. Despite the massive difference in stability, the linear peptide still showed superior antimicrobial activity. The cyclotide and the disulfide-cyclized version demonstrated a slower bactericidal effect than the linear version. All three peptides were stable at high and low pH, and had very low hemolytic and cytotoxic activity.


2004 ◽  
Vol 48 (1) ◽  
pp. 229-235 ◽  
Author(s):  
Masanobu Nishikawa ◽  
Ken'ichi Ogawa

ABSTRACT We have recently developed a convenient method of screening a broad range of microorganisms that produce ε-poly-l-lysine (M. Nishikawa and K. Ogawa, Appl. Environ. Microbiol. 68:3575-3581, 2002). Using this method, we found an ergot fungus that secretes a charged polypeptide other than ε-poly-l-lysine. It was identified as a new species on the basis of its 28S rRNA sequence and was named Verticillium kibiense (formerly Epichloe kibiensis). Peptide sequencing and mass spectrometry revealed that the polypeptide is a linear peptide composed of repeated units of arginyl-histidine. The numbers of repeated units were in most cases five and in some cases four or six. This peptide showed activity against a broad range of bacteria and fungi but lost its activity under conditions of high ionic strength. Zinc and copper ions specifically changed the circular dichroism spectra of the peptide and restored the antimicrobial activity from abrogation under high ionic conditions, although these ions had no reinforcing effect on antimicrobial activity when they were added to solutions at a low ionic strength. The peptide labeled with fluorescein was able to permeate the cell membranes of target microbes, but its ability to permeate cell membranes decreased under conditions of high ionic strength. This decreased ability was partially recovered specifically by the addition of zinc and copper ions. These results indicate that poly(arginyl-histidine) is a cationic polypeptide characterized by specific metal binding and resistance to salts.


Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
L Araujo ◽  
N Padilla ◽  
GG Llanos ◽  
IL Bazzocchi ◽  
L Moujir

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
R Łos ◽  
K Skalicka-Wozniak ◽  
J Widelski ◽  
A Malm ◽  
K Głowniak

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
I Kosalec ◽  
M Zovko ◽  
K Sankovic ◽  
D Kremer ◽  
S Pepeljnjak

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
SN Ebrahimi ◽  
M Yousefzadi ◽  
A Sonboli ◽  
F Miraghasi ◽  
S Ghiasi ◽  
...  

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
T Milošević ◽  
N Nićiforović ◽  
V Mihailović ◽  
S Solujić ◽  
N Vuković

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