Macrocyclic α helical peptide therapeutic modality: A perspective of learnings and challenges
| Autor: | Yaw Sing Tan, Andrea M. Peier, Anthony W. Partridge, Hung Yi Kristal Kaan, Laura Surdi, Tsz Ying Yuen, Tomi K. Sawyer, Srinivasaraghavan Kannan, Shiying Chen, Berengere Sauvagnat, Jerome Hochman, Shuhui Lim, Peter J. Dandliker, Chandra S. Verma, David P. Lane, Pietro G. A. Aronica, Christopher J. Brown, Charles W. Johannes, Simon Ng, Yu-Chi Juang, Brad Sherborne, Fernando J. Ferrer, Sookhee Ha |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation alpha-Helical Macrocyclic Compounds Clinical Biochemistry Pharmaceutical Science Peptide Computational biology 010402 general chemistry 01 natural sciences Biochemistry 03 medical and health sciences Protein structure Basic research Drug Discovery Animals Humans Molecular Biology chemistry.chemical_classification Modality (human–computer interaction) Chemistry Organic Chemistry Ligand (biochemistry) 0104 chemical sciences 030104 developmental biology α helical Molecular Medicine Peptide drug Peptides Intracellular |
| Zdroj: | Bioorganicmedicinal chemistry. 26(10) |
| ISSN: | 1464-3391 |
| Popis: | Macrocyclic α-helical peptides have emerged as a compelling new therapeutic modality to tackle targets confined to the intracellular compartment. Within the scope of hydrocarbon-stapling there has been significant progress to date, including the first stapled α-helical peptide to enter into clinical trials. The principal design concept of stapled α-helical peptides is to mimic a cognate (protein) ligand relative to binding its target via an α-helical interface. However, it was the proclivity of such stapled α-helical peptides to exhibit cell permeability and proteolytic stability that underscored their promise as unique macrocyclic peptide drugs for intracellular targets. This perspective highlights key learnings as well as challenges in basic research with respect to structure-based design, innovative chemistry, cell permeability and proteolytic stability that are essential to fulfill the promise of stapled α-helical peptide drug development. |
| Databáze: | OpenAIRE |
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