Lasso peptides: chemical approaches and structural elucidation

The discovery and development of novel constrained peptides that combine the advantages of therapeutic proteins with those of small molecules has partially prompted the re-emergence of peptides as therapeutics. In this regard, lasso peptides are characterized by both the selectivity and potency of l...

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Published inOrganic & biomolecular chemistry Vol. 16; no. 28; pp. 565 - 58
Main Authors Martin-Gómez, Helena, Tulla-Puche, Judit
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 2018
Subjects
Bioavailability
Biopharmaceuticals
Chemical synthesis
Drug discovery
Immunogenicity
Molecular chains
Organic chemistry
Peptides
Proteins
Proteolysis
Stability
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Summary:The discovery and development of novel constrained peptides that combine the advantages of therapeutic proteins with those of small molecules has partially prompted the re-emergence of peptides as therapeutics. In this regard, lasso peptides are characterized by both the selectivity and potency of larger protein biologics but with no or low immunogenicity, and the stability and bioavailability of small molecules. Moreover, the diverse functionality of lasso peptides and their extraordinary stability against chemical, thermal and proteolytic degradation make them attractive candidates for drug discovery. However, the chemical synthesis of lasso peptides remains a challenge due to the difficulty in building and maintaining their threaded structure. From a therapeutic point of view, these small and constrained structures would provide a new paradigm in drug discovery. The diverse functionality and the extraordinary stability of lasso peptides make these molecules attractive scaffolds for drug discovery. The ability to generate lasso peptides chemically remains a challenging endeavor.
Bibliography:Helena Martín-Gómez received her B.Sc. in Chemistry and a M.Sc. in Organic Chemistry from the University of Barcelona between 2008 and 2013. In 2014 she joined the group of Fernando Albericio as a PhD student and in 2018 she obtained her PhD under guidance of Judit Tulla-Puche at the Institute for Research in Biomedicine (IRB) in Barcelona. Her research interest focuses on peptide chemistry based on natural products and their further biological evaluation.
Judit Tulla Puche received her Ph.D. in organic chemistry from the University of Minnesota under the supervision of Prof. George Barany. Her thesis dealt with the solid-phase synthesis of small proteins. After finishing her doctoral studies, she joined the group of Prof. Fernando Albericio at the Institute for Research in Biomedicine (IRB) where she became Research Associate, working on the synthesis of marine antitumor depsipeptides and complex peptides. In 2015, and after obtaining a Ramon y Cajal contract, she moved to the Department of Organic Chemistry at the University of Barcelona to establish her own research group. Her research interests span a broad range of topics at the interfaces of peptide chemistry and chemical biology.
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ISSN:1477-0520
1477-0539
DOI:10.1039/c8ob01304g