Studying the chemical reactivity properties of the target tumor-environment tripeptides NGR (asparagine-glycine-arginine) and RGD (arginine-glycine-aspartic acid) in their interactions with tamoxifen through conceptual density functional theory.

Abstract

Here, we report theoretical research into the interaction of the drug tamoxifen drug with tripeptides found in the tumor environment-specifically, asparagine-glycine-arginine (NGR) and arginine-glycine-aspartic acid (RGD). Reactivity parameters of these tripeptides were calculated and their intrinsic reactivities and cross-reactivities were analyzed. The interactions of the tripeptides with the nanodiamond-tamoxifen (ND-TAM) complex where the nanodiamond acts as a nanocarrier were also examined theoretically. In addition, their intestinal absorption was predicted based on the polar surface area. The results showed that tamoxifen interacts with RGD, and this interaction remained after the addition of the nanodiamond. An analysis of the chemical hardnesses of the tripeptides was carried out to explore their possible use as synthetic vectors when joined to the nanodiamond. Results indicated that NGR is the most stable of the tripeptides and could be used for active targeting. All calculations were implemented using the conceptual framework of density functional theory.

• Authors: Linda-Lucila Landeros-Martínez, Daniel Glossman-Mitnik, Norma Flores-Holguín
• Journal: Journal of molecular modeling (J Mol Model) Vol. 24 Issue 12 Pg. 336 (Nov 09 2018) ISSN: 0948-5023 [Electronic] Germany
• PMID: 30413890 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Nanodiamonds
• Oligopeptides
• asparagine-glycine-arginine
• Tamoxifen
• arginyl-glycyl-aspartic acid

Topics

• Antineoplastic Agents, Hormonal (chemistry, metabolism, pharmacokinetics)
• Cell Survival (drug effects)
• Density Functional Theory
• Drug Liberation (drug effects)
• Humans
• Models, Molecular
• Nanodiamonds (administration & dosage, chemistry)
• Neoplasms (chemistry, metabolism, pathology)
• Oligopeptides (chemistry, metabolism, pharmacokinetics)
• Protein Binding (drug effects)
• Tamoxifen (chemistry, metabolism, pharmacokinetics)
• Thermodynamics
• Tumor Microenvironment (drug effects)