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Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips

1
Gene Delivery Laboratory, Faculty of pharmacy, Université de Montréal, H3C 3J7, Montréal, QC, Canada
2
Univ. Bordeaux, ARNA Laboratory, F-33016 Bordeaux, France; INSERM U1212, CNRS UMR 5320, ARNA Laboratory, F-33016 Bordeaux, France
*
Author to whom correspondence should be addressed.
Academic Editor: Sébastien Ulrich
Molecules 2019, 24(9), 1803; https://doi.org/10.3390/molecules24091803
Received: 2 April 2019 / Revised: 3 May 2019 / Accepted: 7 May 2019 / Published: 9 May 2019
(This article belongs to the Special Issue Biomolecular Self-Assemblies)
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Abstract

Synthetic acyclic receptors, composed of two arms connected with a spacer enabling molecular recognition, have been intensively explored in host-guest chemistry in the past decades. They fall into the categories of molecular tweezers, clefts and clips, depending on the geometry allowing the recognition of various guests. The advances in synthesis and mechanistic studies have pushed them forward to pharmaceutical applications, such as neurodegenerative disorders, infectious diseases, cancer, cardiovascular disease, diabetes, etc. In this review, we provide a summary of the synthetic molecular tweezers, clefts and clips that have been reported for pharmaceutical applications. Their structures, mechanism of action as well as in vitro and in vivo results are described. Such receptors were found to selectively bind biological guests, namely, nucleic acids, sugars, amino acids and proteins enabling their use as biosensors or therapeutics. Particularly interesting are dynamic molecular tweezers which are capable of controlled motion in response to an external stimulus. They proved their utility as imaging agents or in the design of controlled release systems. Despite some issues, such as stability, cytotoxicity or biocompatibility that still need to be addressed, it is obvious that molecular tweezers, clefts and clips are promising candidates for several incurable diseases as therapeutic agents, diagnostic or delivery tools. View Full-Text
Keywords: molecular tweezers; molecular switches; clefts; clips; responsive systems; drug delivery; biosensing; imaging; controlled release molecular tweezers; molecular switches; clefts; clips; responsive systems; drug delivery; biosensing; imaging; controlled release
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Mbarek, A.; Moussa, G.; Leblond Chain, J. Pharmaceutical Applications of Molecular Tweezers, Clefts and Clips. Molecules 2019, 24, 1803.

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