Abstract
Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers.
Highlights
Biomimetics is the implementation of principles from Nature to the development of new materials or systems
We have studied at structural level the most frequent amino acids observed in the contact zones of protein-DNA complexes: Arginine and Lysine
Data of hydrogen bonds and van der Waals (vdW) interactions in the protein-DNA complexes between each amino acid and phosphate groups (P), deoxyriboses (S) and each type of nitrogenous base: adenine (A), cytosine (C), guanine (G) and thymine (T) are described in detail in Table A in S1 File. Analysis of these results indicates that approximately 65% of the total number of hydrogen bonds established between amino acid residues and DNA occurs with phosphate groups, 23% with nitrogenous bases, and about 12% with deoxyribose
Summary
Biomimetics is the implementation of principles from Nature to the development of new materials or systems. Evolutionary pressure has driven the optimization of efficiency in natural systems; it is valuable to use this knowledge as a source of inspiration to solve existing problems[1]. One of the areas that can benefit from biomimetics is nanomedicine, which provides platforms to understand, build and use structures with biomedical applications at nanometric scale. From Bioinformatics to Rational Design of Dendrimers as Gene Carriers. Initiative of the Ministerio de Economía, Fomento y Turismo
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