Proteins unspecific interactions

Interact with the lipoplex amines still available for protein unspecific interactions, reducing the holes left by the PEG moiety (Scheme 1). 

Flavonoids and other polyphenols can interact with lipids and proteins. The interactions with proteins could be both unspecific or specific, meanwhile the interactions with lipids seems to be rather unspecific, based essentially on physical adsorption. This physical adsorption would mostly depend on the hydrophobic/hydrophilic characteristics of the flavonoid molecule, the number of hydroxyl substituents, and the polymerization degree [Erlejman et al., 2004 Verstraeten et al., 2005, 2003, 2004]. 

To date, the comprehensive measurement of all species in a single live cell over time remains a vision. Nevertheless, conceptual and technical developments in the last decade have enabled progress in two complementary directions. On the one hand, parallel analyses of thousands of species are possible thanks to mass spectrometry and microarrays. Yet, these technologies have the drawbacks that cells have to be disrupted to extract the analytes, and single-cell analyses are still limited by insufficient sensitivity or unspecific interactions, respectively. On the other hand, real-time imaging techniques deliver precise measurements at a single molecule level over time and with high spatial resolution, but are limited to the observations of only a few species at the time (mostly proteins). In both cases, we expect the bottlenecks to be (partially) relieved in the future. 

The same system was used to study the interactions between the polymer mono-layer and a water-soluble protein, bovine serum albumin (BSA) [54]. As could be expected, an increasing amount of PLA in monolayers considerably hindered BSA adsorption, as did the increase of PEO length in the block copolymers. However, many points of this study remain unclear, for example the details of polymer-protein molecular interactions and the protein concentration dependence. No proof was presented that the protein was actually integrated into the monolayer, rather than the interaction being unspecific adsorption (despite PEO-protein repellence), and there was no discussion on the diffusion limit of protein integration. 

However, it is evident that the observed inhibitory effects are non-sequence dependent, and this may be tentatively explained by unspecific interactions with membrane proteins, thus interfering with CD4/Gpl20 interactions. 

At least three regions of the receptor participate in the process of dimer formation. One of them is unspecific and is made up of the sequences of hydrophobic amino acids of the LBD. These form hydrophobic contact surfaces that facilitate, in a general way, the interactions among proteins. The other two are specific sequences of amino acids. One of them is situated immediately after the DBD. It is comprised of a group of some 20 amino acids, and its capacity to intervene in the dimer is independent of binding to the hormone. The other dimerization region is found inside the LBD. It is poorly located, and it is possible that noncontiguous sequences of amino acids participate in it. It is exhibited only when the receptor has been already bound to a hormone. 

Wengler et al. (1982) were able to assemble nucleocapsids of the correct density and size from 42 S RNA and from isolated capsid proteins. Surprisingly, the interaction between the nucleic acid and the capsid protein was found to be fairly unspecific since it was possible to substitute the viral RNA with RNA and DNA molecules ranging in size from... 

With the aim to reduce unspecific protein interactions while controlling DNA release, acid-sensitive PEG has been designed. Several pH-sensitive systems are described in Volume I, Chapter 8. Briefly, the objective is to develop molecules for biological purposes, which means molecules able to be destabilized at slight pH changes. Tumors or ischemia sites present... 

The reactive domains are cleaved from the precursor at a highly conserved repeat domain with the sequence EEKKN. Identification of small quantities of peptides with extended or shortened termini has been taken as an indicator for the involvement of unspecific proteases in the cleavage of the precursor. Structural studies of a Cl-Tl construct derived from the precursor protein using NMR indicate that the domains within the precursor fold independently from each other and that no interdomain interactions are detectable on long-term scale. ... 

Flavonoids, as food components or potential drugs, interact with a wide range of proteins by distinct mechanisms weak and rather unspecific binding of tannins to proline-rich or histi-dine-rich random coils leading to protein precipitation, specific enzyme inhibition, and... 

The distribution and metabolism of protein-based biotech drugs, for example, generally follows the mechanisms of endogenous and nutritional proteins. This includes, for example, unspecific proteolysis as a major elimination pathway for proteins rather than oxidative hepatic metabolism typical for the majority of small-molecule drugs. As a consequence, drug interactions studies focused on cytochrome P-450 enzymes do not usually need to be performed for protein-based biotech drugs [17]. 

There are several recent examples of the switching of nonspecific protein binding on polymer surfaces by application of an external stimulus. Alexander and coworkers demonstrated that protein adhesion can be controlled on PNIPAM surface brushes [14, 181]. For instance, it was reported that the adsorption of FITC-labeled bovine serum albumin (FITC-BSA) on PNIPAM/hexadecanethiol micropatterned surfaces could be tuned by LCST. However, this effect was found to be less pronounced after prolonged incubation times or repeated heating/cooling cycles. The authors suggested that this behavior could be due to unspecific PNIPAM-protein interactions [14],... 

Many approaches comprise some attractive features with respect to specific binding to certain integrins and long-term stability of the produced surface coatings. In order to ensure the exclusive interaction of the cells with the recognition sites presented (and not with unspecifically adsorbed proteins), the matrix (i.e., the background) must possess protein-repellent properties. 

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