Biomimetic engineering of the molecular recognition and self-assembly of peptides and proteins via halogenation
Pizzi, A.a, Pigliacelli, C.a, Bergamaschi, G.b, Gori, A.b, Metrangolo, P.a
a Laboratory of Supramolecular and Bio-Nanomaterials (SBNLab), Department of Chemistry, Materials, and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Via L. Mancinelli 7, Milano, 20131, Italy
b Istituto di Scienze e Tecnologie Chimiche, National Research Council of Italy, Via M. Bianco 9, Milano, 20131, Italy
Halogenation is widespread in Nature, as witnessed by the several thousands of naturally occurring halogenated compounds. This review seeks to provide an overview on the pathways and multiple roles of halogenation in Nature, as a source of inspiration to chemists. Remarkably, several halogenation pathways were recently found in humans, sparking an increasing interest into halogens as biomolecular recognition sites. A description of the molecular mechanisms underlining the role of halogenation in the biomolecular context is provided, highlighting how the strategic use of halogen-driven interactions can be exploited to tune the properties of both small compounds and macromolecules. The complexity, versatility and bio-orthogonality of halogen-driven interactions are indeed key figures of merit in promoting novel opportunities for halogenation in a range of applications, spanning from drug design to self-assembly and biomolecular engineering. Specifically, the most relevant and impactful recent contributions in the field of peptide and protein science are presented and critically discussed, with a particular emphasis on the existing opportunities to control their conformational and self-assembly properties towards novel therapeutics and functional materials.
