Cyclic Analogues of Horseshoe Crab Peptide Tachyplesin I with Anticancer and Cell Penetrating Properties

2019 ◽  
Vol 14 (12) ◽  
pp. 2895-2908
Author(s):  
Felicitas Vernen ◽  
David J. Craik ◽  
Nicole Lawrence ◽  
Sónia Troeira Henriques
2021 ◽  
Author(s):  
Anna S Amiss ◽  
Jessica B von Pein ◽  
Jessica R Webb ◽  
Nicholas D Condon ◽  
Peta J Harvey ◽  
...  

Bacteria that occupy an intracellular niche can evade extracellular host immune responses and antimicrobial molecules. In addition to classic intracellular pathogens, other bacteria including uropathogenic Escherichia coli (UPEC) can adopt both extracellular and intracellular lifestyles. UPEC intracellular survival and replication complicates treatment, as many therapeutic molecules do not effectively reach all components of the infection cycle. In this study, we explored cell penetrating antimicrobial peptides from distinct structural classes as alternative molecules for targeting bacteria. We identified two β-hairpin peptides from the horseshoe crab, tachyplesin I and polyphemusin I, with broad antimicrobial activity toward a panel of pathogenic and non-pathogenic bacteria in planktonic form. Peptide analogues [I11A]tachyplesin I and [I11S]tachyplesin I maintained activity toward bacteria, but were less toxic to mammalian cells than native tachyplesin I. This important increase in therapeutic window allowed treatment with higher concentrations of [I11A]tachyplesin I and [I11S]tachyplesin I, to significantly reduce intramacrophage survival of UPEC in an in vitro infection model. Mechanistic studies using bacterial cells, model membranes and cell membrane extracts, suggest that tachyplesin I and polyphemusin I peptides kill UPEC by selectively binding and disrupting bacterial cell membranes. Moreover, treatment of UPEC with sublethal peptide concentrations increased zinc toxicity and enhanced innate macrophage antimicrobial pathways. In summary, our combined data show that cell penetrating peptides are attractive alternatives to traditional small molecule antimicrobials for treating UPEC infection, and that optimization of native peptide sequences can deliver effective antimicrobials for targeting bacteria in extracellular and intracellular environments.


1989 ◽  
Vol 37 (10) ◽  
pp. 2661-2664 ◽  
Author(s):  
Kenichi AKAJI ◽  
Nobutaka FUJII ◽  
Fuminori TOKUNAGA ◽  
Toshiyuki MIYATA ◽  
Sadaaki IWANAGA ◽  
...  
Keyword(s):  

2013 ◽  
Vol 53 (supplement1-2) ◽  
pp. S215
Author(s):  
Takahiro Kushibiki ◽  
Masakatsu Kamiya ◽  
Tomoyasu Aizawa ◽  
Yasuhiro Kumiki ◽  
Takashi Kikukawa ◽  
...  

Chemotherapy ◽  
1991 ◽  
Vol 37 (5) ◽  
pp. 327-334 ◽  
Author(s):  
Tsukasa Murakami ◽  
Makoto Niwa ◽  
Fuminori Tokunaga ◽  
Toshiyuki Miyata ◽  
Sadaaki Iwanaga

2014 ◽  
Vol 1844 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Takahiro Kushibiki ◽  
Masakatsu Kamiya ◽  
Tomoyasu Aizawa ◽  
Yasuhiro Kumaki ◽  
Takashi Kikukawa ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Hongya Zhao ◽  
Jianguo Dai ◽  
Gang Jin

Tachyplesin I (TP I) is an antimicrobial peptide isolated from the hemocytes of the horseshoe crab. With the developments of DNA microarray technology, the genetic analysis of the toxic effect of TP I on embryo was originally considered in our recent study. Based on our microarray data of the embryonic samples of zebrafish treated with the different doses of TP I, we performed a series of statistical data analyses to explore the toxic effect of TP I at the genomic level. In this paper, we first employed the hexaMplot to illustrate the continuous variation of the gene expressions of the embryonic cells treated with the different doses of TP I. The probabilistic model-based Hough transform was used to classify these differentially coexpressed genes of TP I on the zebrafish embryos. As a result, three line rays supported with the corresponding 174 genes were detected in our analysis. Some biological processes of the featured genes, such as antigen processing, nuclear chromatin, and structural constituent of eye lens, were significantly filtered with the smallerPvalues.


Author(s):  
T. Wichertjes ◽  
E.J. Kwak ◽  
E.F.J. Van Bruggen

Hemocyanin of the horseshoe crab (Limulus polyphemus) has been studied in nany ways. Recently the structure, dissociation and reassembly was studied using electron microscopy of negatively stained specimens as the method of investigation. Crystallization of the protein proved to be possible and X-ray crystallographic analysis was started. Also fluorescence properties of the hemocyanin after dialysis against Tris-glycine buffer + 0.01 M EDTA pH 8.9 (so called “stripped” hemocyanin) and its fractions II and V were studied, as well as functional properties of the fractions by NMR. Finally the temperature-jump method was used for assaying the oxygen binding of the dissociating molecule and of preparations of isolated subunits. Nevertheless very little is known about the structure of the intact molecule. Schutter et al. suggested that the molecule possibly consists of two halves, combined in a staggered way, the halves themselves consisting of four subunits arranged in a square.


2007 ◽  
Author(s):  
Naxin Jiang ◽  
Nguan Soon Tan ◽  
Bow Ho ◽  
Jeak Ling Ding

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