Fixing the Unfixable: The Art of Optimizing Natural Products for Human Medicine
| Autor: | Brian O. Bachmann, Audrey E Ynigez-Gutierrez |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Chemistry
Pharmaceutical Lactams Macrocyclic Chemistry Organic Polyenes 01 natural sciences Natural (archaeology) 03 medical and health sciences chemistry.chemical_compound Synthetic biology Cell Line Tumor Neoplasms Drug Discovery Human medicine Benzoquinones Humans 030304 developmental biology 0303 health sciences Biological Products Natural product Extramural Pactamycin Glycopeptides Total synthesis Semisynthesis 0104 chemical sciences Anti-Bacterial Agents 010404 medicinal & biomolecular chemistry chemistry Tetracyclines Multigene Family Molecular Medicine Synthetic Biology Biochemical engineering Macrolides Peptides |
| Zdroj: | Journal of medicinal chemistry. 62(18) |
| ISSN: | 1520-4804 |
| Popis: | Molecules isolated from natural sources including bacteria, fungi, and plants are a long-standing source of therapeutics that continue to add to our medicinal arsenal today. Despite their potency and prominence in the clinic, complex natural products often exhibit a number of liabilities that hinder their development as therapeutics, which may be partially responsible for the current trend away from natural product discovery, research, and development. However, advances in synthetic biology and organic synthesis have inspired a new generation of natural product chemists to tackle powerful undeveloped scaffolds. In this Perspective, we will present case studies demonstrating the historical and current focus on making targeted, but significant, changes to natural product scaffolds via biosynthetic gene cluster manipulation, total synthesis, semisynthesis, or a combination of these methods, with a focus on increasing activity, decreasing toxicity, or improving chemical and pharmacological properties. |
| Databáze: | OpenAIRE |
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