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1. |
Role of water in protein folding, oligomerization, amyloidosis and miniprotein |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 747-759
Tamás Vajda,
András Perczel,
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摘要:
The essential involvement of water in most fundamental extra‐cellular and intracellular processes of proteins is critically reviewed and evaluated in this article. The role of water in protein behavior displays structural ambivalence; it can protect the disordered peptide‐chain by hydration or helps the globular chain‐folding, but promotes also the protein aggregation, as well (see: diseases). A variety of amyloid diseases begins as benign protein monomers but develops then into toxic amyloid aggregates of fibrils. Our incomplete knowledge of this process emphasizes the essential need to reveal the principles of governing this oligomerization. To understand the biophysical basis of the simplerin vitroamyloid formation may help to decipher also thein vivoway. Nevertheless, to ignore the central role of the water's effect among these events means to receive an uncompleted picture of the true phenomenon. Therefore this review represents a stopgap role, because the most published studies—with a few exceptions—have been neglected the crucial importance of water in the protein research. The following questions are discussed from the water's viewpoint: (i) interactions between water and proteins, (ii) protein hydration/dehydration, (iii) folding of proteins and miniproteins, (iv) peptide/protein oligomerization, and (v) amyloidosis. Copyright © 2014 European Peptide Society and John Wiley
ISSN:1075-2617
DOI:10.1002/psc.2671
年代:2014
数据来源: WILEY
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2. |
Cell penetration: scope and limitations by the application of cell‐penetrating peptides |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 760-784
Siegmund Reissmann,
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摘要:
The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell‐penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored inin vivostudies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging.This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood–brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. Copyright © 2014 European Peptide Society and John Wiley&Sons,
ISSN:1075-2617
DOI:10.1002/psc.2672
年代:2014
数据来源: WILEY
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3. |
Functional properties of a novel hybrid antimicrobial peptide NS: potent antitumor activity and efficient plasmid delivery |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 785-793
Yun Zhang,
Jingjing Song,
Wei Zhang,
Ranran Liang,
Yinyun Ma,
Li Zhang,
Xiaojin Wei,
Jingman Ni,
Rui Wang,
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摘要:
Antimicrobial peptides have been widely recognized as potential candidates for treating tumor, especially for defending against multidrug‐resistant cells. Previously, based on the structure of substance P, we have designed a novel class of hybrid antimicrobial peptide NS, which possesses potent antimicrobial activity against a broad spectrum of bacterial pathogens. In this study, we evaluated its cytotoxicity to tumor cells and studied the possible mechanism of action. We showed that NS could efficiently kill tumor cells by rapidly disrupting the tumor cell membrane and inhibiting the DNA synthesis. In addition, we also found that NS could efficiently deliver plasmids into cells and exhibit high transfection efficiency after the introduction of a stearyl moiety to its N‐terminus, like many reported cell‐penetrating peptides. Taken together, this study revealed the potential multiple functions of NS, providing fundamental support for further therapeutic application as potential antitumor agent. Copyright © 2014 European Peptide Society and John Wiley&Son
ISSN:1075-2617
DOI:10.1002/psc.2667
年代:2014
数据来源: WILEY
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4. |
Modulating the structure of phenylalanine‐incorporated ascidiacyclamide through fluorination |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 794-802
Akiko Asano,
Takeshi Yamada,
Mitsunobu Doi,
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摘要:
We designed four fluorinated Phe‐incorporated ascidiacyclamide ([Phe]ASC) analogs, (cyclo(−Xxx1‐oxazoline2‐d‐Val3‐thiazole4‐Ile5‐oxazoline6‐d‐Val7‐thiazole8‐)), [(4‐F)Phe]ASC (Xxx1: 4‐fluorophenylalanine), [(3,5‐F2)Phe]ASC (Xxx1: 3,5‐difluorophenylalanine), [(3,4,5‐F3)Phe]ASC (Xxx1: 3,4,5‐trifluorophenylalanine) and [(F5)Phe]ASC (Xxx1: pentafluorophenylalanine), to modulate theπ‐electron density of the aromatic ring of the Phe residue. X‐ray diffraction analysis,1H NMR and CD spectra all suggested that the interactions between the benzene ring of the Xxx1 residue and the alkyl groups of oxazoline2 contribute to the stability of the folded structure of these analogs. Substituting fluorines for the hydrogens progressively weakened those interactions through reducing theπ‐electron density, thereby mediating transformation from the folded to square structure. As a result, [(F5)Phe]ASC preferred the square form more than the other analogs did. Also contributing to the preference for the square form may be the hindrance of the rotation around the Cα–Cβbond by the two ortho‐fluoro substituents of [(F5)Phe]ASC. These findings demonstrate that the structure of ASC can be modulated by using fluorine as an electron‐withdrawing group. Copyright © 20
ISSN:1075-2617
DOI:10.1002/psc.2668
年代:2014
数据来源: WILEY
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5. |
The effect of LfcinB9 on human ovarian cancer cell SK‐OV‐3 is mediated by inducing apoptosis |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 803-810
Minjia Sheng,
Yanjie Zhao,
Aichen Zhang,
Liyan Wang,
Guizhen Zhang,
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摘要:
LfcinB9 is a peptide derived from lactoferricin B. In the present study, the effect and relative mechanism of LfcinB9 on human ovarian cancer cell line (SK‐OV‐3)in vitroandin vivowas investigated. The data obtained indicated that LfcinB9 exhibited low hemolysis activity and significantly inhibited the proliferation of SK‐OV‐3 cellsin vitro. In addition, the apoptosis of SK‐OV‐3 cells was induced through up‐regulating the production of reactive oxygen species and activating caspase‐3, caspase‐9 on both transcription and translation level. Finally, LfcinB9 significantly prevented the tumor growth in the SK‐OV‐3‐bearing mice model. These results indicated that LfcinB9 could be a potential agent for the treatment of ovarian cancer. Copyright © 2014 European Peptide Society
ISSN:1075-2617
DOI:10.1002/psc.2670
年代:2014
数据来源: WILEY
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6. |
Micelle bound structure and DNA interaction of brevinin‐2‐related peptide, an antimicrobial peptide derived from frog skin |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 811-821
Susmita Bandyopadhyay,
Boon Yee Ng,
Charmaine Chong,
Ming Zhen Lim,
Sonia Kiran Gill,
Ke Hui Lee,
J Sivaraman,
Chiradip Chatterjee,
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摘要:
Brevinin‐2‐related peptide (BR‐II), a novel antimicrobial peptide isolated from the skin of frog,Rana septentrionalis, shows a broad spectrum of antimicrobial activity with low haemolytic activity. It has also been shown to have antiviral activity, specifically to protect cells from infection by HIV‐1. To understand the active conformation of the BR‐II peptide in membranes, we have investigated the interaction of BR‐II with the prokaryotic and eukaryotic membrane‐mimetic micelles such as sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC), respectively. The interactions were studied using fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments revealed that the N‐terminus tryptophan residue of BR‐II interacts with the hydrophobic core of the membrane mimicking micelles. The CD results suggest that interactions with membrane‐mimetic micelles induce anα‐helix conformation in BR‐II. We have also determined the solution structures of BR‐II in DPC and SDS micelles using NMR spectroscopy. The structural comparison of BR‐II in the presence of SDS and DPC micelles showed significant conformational changes in the residues connecting the N‐terminus and C‐terminus helices. The ability of BR‐II to bind DNA was elucidated by agarose gel retardation and fluorescence experiments. The structural differences of BR‐II in zwitterionic versus anionic membrane mimics and the DNA binding ability of BR‐II collectively contribute to the general understanding of the pharmacological specificity of this peptide towards prokaryotic and eukaryotic membranes and provide insights into its overall antimicrobial mechanism. Copyright © 2014 European P
ISSN:1075-2617
DOI:10.1002/psc.2673
年代:2014
数据来源: WILEY
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7. |
Antibacterial and anti‐inflammatory activity of a temporin B peptide analogue on anin vitromodel of cystic fibrosis |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page 822-830
Valentino Bezzerri,
Concetta Avitabile,
Maria Cristina Dechecchi,
Ilaria Lampronti,
Monica Borgatti,
Giulia Montagner,
Giulio Cabrini,
Roberto Gambari,
Alessandra Romanelli,
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摘要:
Natural peptides with antimicrobial properties are deeply investigated as tools to fight bacteria resistant to common antibiotics. Small peptides, as those belonging to the temporin family, are very attractive because their activity can easily be tuned after small modification to their primary sequence. Structure‐activity studies previously reported by us allowed the identification of one peptide, analogue of temporin B, TB_KKG6A, showing, unlike temporin B, antimicrobial activity against both Gram‐positive and Gram‐negative bacteria. In this paper, we investigated the antimicrobial and anti‐inflammatory activity of the peptide TB_KKG6A againstPseudomonas aeruginosa. Interestingly, we found that the peptide exhibits antimicrobial activity at low concentrations, being able to downregulate the pro‐inflammatory chemokines and cytokines interleukin (IL)‐8, IL‐1β, IL‐6 and tumor necrosis factor‐αproduced downstream infected human bronchial epithelial cells. Experiments were carried out also with temporin B, which was found to show pro‐inflammatory activity. Details on the interaction between TB_KKG6A and theP. aeruginosaLPS were obtained by circular dichroism and fluorescence studies. Copyright © 2014 European Peptide Society an
ISSN:1075-2617
DOI:10.1002/psc.2674
年代:2014
数据来源: WILEY
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8. |
Issue information |
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Journal of Peptide Science,
Volume 20,
Issue 10,
2014,
Page -
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ISSN:1075-2617
DOI:10.1002/psc.2565
年代:2014
数据来源: WILEY
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