Moura, LIF;
Martinho, N;
Silva, LC;
Barata, TS;
Brocchini, S;
Florindo, HF;
Zloh, M;
(2017)
Poly-glutamic dendrimer-based conjugates for cancer vaccination – a computational design for targeted delivery of antigens.
Journal of Drug Targeting
, 25
(9-10)
pp. 873-880.
10.1080/1061186X.2017.1363213.
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Abstract
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds. When the number of mannosamines conjugated to dendrimer was increased from 16 to 32, the dendrimer interacted with the receptor with higher affinity. However, 16 mannosamines-NBD-PG-G4-dendrimer was chosen to conjugate TAA for added functionality as no carboxylic end groups were available for further conjugation in the 32 mannosamines-dendrimer. Docking results showed that the majority of TAA-conjugated NBD-PG-G4-dendrimer demonstrated a favourable interaction with mannosamine binding site on mannose receptor, thus constituting a promising tool for TAA targeted delivery. Our in silico approach effectively narrows down the selection of the best candidates for the synthesis of functionalised PG-dendrimers with desired functionalities. These results will significantly reduce the time and efforts required to experimentally synthesise modified dendrimers for optimal antigen delivery.
| Type: | Article |
|---|---|
| Title: | Poly-glutamic dendrimer-based conjugates for cancer vaccination – a computational design for targeted delivery of antigens |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/1061186X.2017.1363213 |
| Publisher version: | http://dx.doi.org/10.1080/1061186X.2017.1363213 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Peptide dendrimer, poly(glutamic acid), computational design, molecular dynamics simulation, receptor docking, tumour associated antigens, immunotherapy, cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1570407 |
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