scholarly journals Interaction of polyamidoamine dendrimers and amphiphylic dendrons with lipid membranes

Author(s):  
M. M. Terehova ◽  
V. M. Abashkin ◽  
V. A. Zhogla ◽  
I. V. Halets-Bui ◽  
S. Zh. Loznikova ◽  
...  

Polyamidoamine (PAMAM) dendrimers and amphiphilic dendrons are one of the types of nanomaterials characterized by a hyperbranched structure of polymer branches. In the case of dendrimers, the dendrons are covalently linked at the central focal point. In the case of amphiphilic dendrons, dendrons are non-covalently linked by hydrophobic interactions, forming micellar structures. These nanoparticles are widely used in biology and medicine as contrast agents, carriers of drugs and genetic material. Their use in scientific practice requires an understanding of the basic mechanisms of their interaction with membranes – the main obstacle to the entry of dendrimers into the cell. This review discusses the regularities of the interaction of dendrimers and amphiphilic dendrons with lipid membranes. Various models of dendrimer-membrane interactions are described as the basis for the penetration of dendrimers and amphiphilic nanoparticles into cells. Keywords: polyamidoamine dendrimers, amphiphilic dendrons, lipid membranes, cells, antitumor therapeutics, antibacterial agents, diagnostics, genetic therapy.

2018 ◽  
Vol 14 ◽  
pp. 2646-2650 ◽  
Author(s):  
Abed Tarapdar ◽  
James K S Norris ◽  
Oliver Sampson ◽  
Galina Mukamolova ◽  
James T Hodgkinson

Siderophore–antibiotic conjugates consist of an antibiotic covalently linked by a tether to a siderophore. Such conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and latent TB. Herein we report the design and synthesis of the first phenothiazine–siderophore conjugate. A convergent synthetic route was developed whereby the functionalised phenothiazine component was prepared in four steps and the siderophore component also prepared in four steps. In M. smegmatis the functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore–phenothiazine conjugates for full biological evaluation of much needed new antibacterial agents.


2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Chi L. L. Pham ◽  
Roberto Cappai

The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.


2005 ◽  
Vol 35 (5) ◽  
pp. 1173-1182 ◽  
Author(s):  
Kevin A Crowe ◽  
William H Parker

This study was a first attempt to model the problem of delineating breeding zones as a maximal covering location problem. The method involves two steps. First, a comprehensive set of candidate breeding zones is generated for a region using the focal point seed zone method. This method allows for control over the adaptive difference of genetic material within each zone. A grid of points is used to create the set of candidate breeding zones: one zone per point. Next, candidate zones are entered into a maximal covering location model formulated to suit this problem. The objective of this model is to select a subset of candidate zones that maximally covers the area of the region, given a limit on the number of zones to be selected and on the adaptive dissimilarity allowed within zones. Through use of this method, decision-makers can gain insight into how many breeding zones are needed to cover the region. Using different inputs from the focal point seed zone method, it is also possible to explore the trade-offs between the quantity and the quality of breeding zones. The method was tested on data from a series of jack pine (Pinus banksiana Lamb.) common garden trials of 102 seed sources from northwestern Ontario.


1994 ◽  
Vol 59 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Zhi‐Chu Bi ◽  
Yue‐Ying Qian ◽  
Xin‐Li Zhao ◽  
Shu‐Yin Shen ◽  
Jia‐Yong Yu ◽  
...  

1982 ◽  
Vol 20 (2) ◽  
pp. 139-151 ◽  
Author(s):  
N.B. Joshi ◽  
J.R. Lopez ◽  
H.T. Tien ◽  
Ching-Bore Wang ◽  
Qi-Yi Liu

2016 ◽  
Vol 7 ◽  
pp. 524-532 ◽  
Author(s):  
Dorota Matyszewska

In this work the interactions of an anticancer drug daunorubicin (DNR) with model thiolipid layers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE) were investigated using Langmuir technique. The results obtained for a free drug were compared with the results recorded for DNR attached to SWCNTs as potential drug carrier. Langmuir studies of mixed DPPTE–SWCNTs-DNR monolayers showed that even at the highest investigated content of the nanotubes in the monolayer, the changes in the properties of DPPTE model membranes were not as significant as in case of the incorporation of a free drug, which resulted in a significant increase in the area per molecule and fluidization of the thiolipid layer. The presence of SWCNTs-DNR in the DPPTE monolayer at the air–water interface did not change the organization of the lipid molecules to such extent as the free drug, which may be explained by different types of interactions playing crucial role in these two types of systems. In the case of the interactions of free DNR the electrostatic attraction between positively charged drug and negatively charged DPPTE monolayer play the most important role, while in the case of SWCNTs-DNR adducts the hydrophobic interactions between nanotubes and acyl chains of the lipid seem to be prevailing. Electrochemical studies performed for supported model membranes containing the drug delivered in the two investigated forms revealed that the surface concentration of the drug-nanotube adduct in supported monolayers is comparable to the reported surface concentration of the free DNR incorporated into DPPTE monolayers on gold electrodes. Therefore, it may be concluded that the application of carbon nanotubes as potential DNR carrier allows for the incorporation of comparable amount of the drug into model membranes with simultaneous decrease in the negative changes in the membrane structure and organization, which is an important aspect in terms of side effects of the drug.


1996 ◽  
Vol 93 (10) ◽  
pp. 4897-4902 ◽  
Author(s):  
J. F. Kukowska-Latallo ◽  
A. U. Bielinska ◽  
J. Johnson ◽  
R. Spindler ◽  
D. A. Tomalia ◽  
...  

2014 ◽  
Vol 27 (4) ◽  
pp. 709-744 ◽  
Author(s):  
Liesbet De Kock

ArgumentThis paper aims at contributing to the ongoing efforts to get a firmer grasp of the systematic significance of the entanglement of idealism and empiricism in Helmholtz's work. Contrary to existing analyses, however, the focal point of the present exposition is Helmholtz's attempt to articulate a psychological account of objectification. Helmholtz's motive, as well as his solution to the problem of the object are outlined, and interpreted against the background of his scientific practice on the one hand, and that of empiricist and (transcendental) idealist analyses of experience on the other. The specifically psychological angle taken, not only prompts us to consider figures who have hitherto been treated as having only minor import for Helmholtz interpretation (most importantly J.S. Mill and J.G. Fichte), it furthermore sheds new light on some central tenets of the latter's psychological stance that have hitherto remained underappreciated. For one thing, this analysis reveals an explicit voluntarist tendency in Helmholtz's psychological theory. In conclusion, it is argued that the systematic significance of Helmholtz's empirico-transcendentalism with respect to questions of the mind is best understood as an attempt to found his empirical theory of perception in a second order, normative account of epistemic subjectivity.


1994 ◽  
Vol 14 (1) ◽  
pp. 15-24 ◽  
Author(s):  
João Ramalho-Santos ◽  
Ricardo Negrão ◽  
Maria da Conceição Pedroso de Lima

We have studied the role of hydrophobic interactions in the fusion activity of two lipid enveloped viruses, influenza and Sendai. Using the fluorescent probe ANS (1-aminonaphtalene-8-sulfonate) we have shown that low-pH-dependent influenza virus activation involves a marked increase in the viral envelope hydrophobicity. The effect of dehydrating agents on the fusion activity of both viruses towards model lipid membranes was studied using a fluorescence dequenching assay. Dehydrating agents such as dimethylsulfoxide and dimethylsulfone greatly enhanced the initial rate of the fusion process, the effect of dimethylsulfone doubling that of dimethylsulfoxide. The effect of poly(ethylene glycol) on the fusion process was found to be dependent on the polymer concentration and molecular weight. In general, similar observations were made for both viruses. These results stress the importance of dehydration and hydrophobic interactions in the fusion activity of influenza and Sendai viruses, and show that these factors may be generally involved in membrane fusion events mediated by many other lipid enveloped viruses.


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