Icosahedral boron clusters as modifying entities for biomolecules

ABSTRACT

Introduction: Icosahedral boron clusters have unique properties useful in medicinal chemistry: rigidity, chemical stability, and three-dimensional aromaticity. Furthermore, these abiotic compounds have low toxicity and are stable in the biological environment. All these features ultimately give them the ability to interact with biological molecules in a different mode than organic compounds.

Areas covered: In the present article, we aim to introduce boron clusters as a class of entities suitable for modifications of biomolecules to obtain a specific biological effect. We will focus on icosahedral boron clusters, as well as metallacarboranes, and their biological activity and interaction with the biological environment.

Expert opinion: Boron clusters are suitable for altering structural and functional features of biomolecules and can be used in the development of new drugs and drug delivery systems. The high affinity of boron clusters, especially metallacarboranes, to albumin creates a new possibility to use them to optimize the pharmacokinetics of biologically active peptides. Boron clusters have high potential in biological and medicinal applications. Due to their peculiar properties, they can be used to optimize parameters critical for the biological activity of therapeutic substances and their affinity toward biological targets.

KEYWORDS:

• Boron clusters
• boron neutron capture therapy
• conjugates
• dicarbollides
• metallacarboranes

Article highlights

• The abiotic character of icosahedral boron clusters is a potentially useful feature because therapeutic biomolecules containing these clusters may be more stable in the biological environment and may be less prone to the development of resistance.

• The unique interaction properties of boron clusters and their derivatives with biomolecules, different than those between carbon-based molecules, offer novel features in potential drug targeting.

• Interactions of selected boron clusters and their derivatives with serum albumin create new opportunities for the use of these cages as anchors to albumin for therapeutic biomolecules, prolonging their half-life and tuning pharmacokinetics.

• Attachment of lipophilic carborane to a hydrophilic peptide confers amphiphilic properties to the pseudopeptide analog and the ability to transmigrate through biological membranes, which allows topical instead of intravenous administration of peptide drugs.

• In vivo and in vitro experiments showed that boron clusters have low toxicity; therefore, they are safe to use as drug components.

• Development of the reaction of the nucleophilic ring-opening of cyclic oxonium derivatives of boron clusters opens a new way for preparation of a rich family of boron clusters containing biologically active conjugates.

This box summarizes key points contained in the article.

Acknowledgments

Part of the content of this paper was presented at Fifth International Symposium on Thymosins in Health and Disease and is part of a supplement issue funded by SciClone Pharmaceuticals

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

TM Goszczyński is funded by grant number 2016/23/D/NZ1/02611, National Science Centre, Poland, New strategies in cancer therapy — bioinorganic conjugates of cytostatics and boron clusters. K Fink and J Boratyński are funded by grant number 2015/19/N/NZ7/02726, National Science Centre, Poland, Synthesis, physicochemical and biological properties of thymosin beta4 - boron cluster conjugates. New strategy of improvement of pharmacokinetic parameters of therapeutic peptides. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.