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Structural diversity of bicyclic amino acids

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Summary.

Over the years biomedical research has been constantly oriented towards the development of new therapeutics based on bioactive peptides and their analogues. In particular, the generation of compounds having structures and functions similar to bioactive peptides, named “peptidomimetics”, raised much interest among organic and medicinal chemists due to the possibility by using such compounds to improve both potency and stability of peptidic lead compounds. In the context of this research area, unnatural amino acids are of great interest in drug discovery, and their use as new building blocks for the development of peptidomimetics with high diversity level and possessing high-ordered structures is of special interest. In particular, medicinal chemistry has taken advantage of the use of amino acid homologues and of cyclic and polycyclic templates to introduce elements of diversity for the generation of new molecules as drug candidates. Bicyclic amino acids have been developed as reverse turn mimetics and dipeptide isosteres, and the constraint imposed by their structures has been reported as a tool for controlling the conformational preferences of modified peptides. Moreover, synthetic efforts have been driven to the generation of diverse structures based on the modulation of ring size and scaffold decoration by suitable functional groups. Herein is reported an overview of different classes of bicyclic amino acids, taking into account the strategies to achieve structurally diverse templates, and some implications in medicinal chemistry are also disclosed.

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  1. Dipartimento di Chimica Organica “Ugo Schiff” and Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Bioattivi (HeteroBioLab), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, Sesto Fiorentino, Firenze, Italy

    A. Trabocchi, D. Scarpi & A. Guarna

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  1. A. Trabocchi
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  2. D. Scarpi
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  3. A. Guarna
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Correspondence to A. Guarna.

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Authors’ address: Antonio Guarna, Dipartimento di Chimica Organica “Ugo Schiff” and Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Bioattivi (HeteroBioLab), Università degli Studi di Firenze, Polo Scientifico e Tecnologico, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Firenze, Italy

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Trabocchi, A., Scarpi, D. & Guarna, A. Structural diversity of bicyclic amino acids. Amino Acids 34, 1–24 (2008). https://doi.org/10.1007/s00726-007-0588-y

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