| Title |
Rational design of novel, fluorescent, tagged glutamic acid dendrimers with different terminal groups and in silico analysis of their properties
|
|---|---|
| Published in |
International Journal of Nanomedicine, September 2017
|
| DOI | 10.2147/ijn.s135475 |
| Pubmed ID | |
| Authors |
Nuno Martinho, Liana C Silva, Helena F Florindo, Steve Brocchini, Mire Zloh, Teresa S Barata |
| Abstract |
Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure-activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level. However, these probes can change dendrimer surface properties and have a direct impact on their interactions with biomolecules and with lipid membranes. In this study, we have used computer-aided molecular design and molecular dynamics simulations to identify optimal topology of a poly(l-glutamic acid) (PG) backbone dendrimer that allows incorporation of fluorophores in the core with minimal availability for undesired interactions. Extensive all-atom molecular dynamic simulations with the CHARMM force field were carried out for different generations of PG dendrimers with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green 488) and various surface groups (glutamic acid, lysine and tryptophan). Analysis of structural and topological features of all designed dendrimers provided information about their size, shape, internal distribution and dynamic behavior. We have found that four generations of a PG dendrimer are needed to ensure minimal exposure of a core-conjugated fluorophore to external environment and absence of undesired interactions regardless of the surface terminal groups. Our findings suggest that NBD-PG-G4 can provide a suitable scaffold to be used for biophysical studies of surface-modified dendrimers to provide a deeper understanding of their intermolecular interactions, mechanisms of action and trafficking in a biological system. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 32 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 19% |
| Student > Ph. D. Student | 6 | 19% |
| Professor | 3 | 9% |
| Student > Master | 2 | 6% |
| Librarian | 2 | 6% |
| Other | 5 | 16% |
| Unknown | 8 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 9 | 28% |
| Medicine and Dentistry | 3 | 9% |
| Computer Science | 2 | 6% |
| Biochemistry, Genetics and Molecular Biology | 2 | 6% |
| Agricultural and Biological Sciences | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 13 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 October 2017.
All research outputs
#22,764,772
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#3,598
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#284,752
of 324,453 outputs
Outputs of similar age from International Journal of Nanomedicine
#89
of 102 outputs
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