Dynamical interactions of 5-fluorouracil drug with dendritic peptide vectors: the impact of dendrimer generation, charge, counterions, and structured water

De Luca, Sergio, Seal, Prasenjit, Ouyang, Defang, Parekh, Harendra S., Kannam, Sridhar Kumar and Smith, Sean C. (2016) Dynamical interactions of 5-fluorouracil drug with dendritic peptide vectors: the impact of dendrimer generation, charge, counterions, and structured water. Journal of Physical Chemistry B, 120 25: 5732-5743. doi:10.1021/acs.jpcb.6b00533


Author De Luca, Sergio
Seal, Prasenjit
Ouyang, Defang
Parekh, Harendra S.
Kannam, Sridhar Kumar
Smith, Sean C.
Title Dynamical interactions of 5-fluorouracil drug with dendritic peptide vectors: the impact of dendrimer generation, charge, counterions, and structured water
Journal name Journal of Physical Chemistry B   Check publisher's open access policy
ISSN 1520-5207
1520-6106
Publication date 2016-06-30
Year available 2016
Sub-type Article (original research)
DOI 10.1021/acs.jpcb.6b00533
Open Access Status Not yet assessed
Volume 120
Issue 25
Start page 5732
End page 5743
Total pages 12
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2017
Language eng
Abstract Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution.
Keyword Molecular dynamics simulations
5-fluorouracil (5FU)
Skin cancer drug
Peptide-based dendritic carrier systems
Drug−carrier interactions
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
 
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