title: Making a Long Journey Short: Alkyne Functionalization of Natural Product Scaffolds.
abstract: Biological selection makes natural products promising scaffolds for drug development and the ever growing number of newly identified, structurally diverse molecules helps to fill the gaps in chemical space. Elucidating the function of a small molecule, such as identifying its protein binding partners, its on- and off-targets, is becoming increasingly important. Activity- and affinity-based protein profiling are modern strategies to acquire such molecular-level information. Introduction of a molecular handle (azide, alkyne, biotin) can shed light on the mode of action of small molecules. This Concept article covers central points on synthetic methodology for integrating a terminal alkyne into a molecule of interest.
authors.affiliation: Center for Integrated Protein Science, Munich (CIPSM), Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747, Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Center for Integrated Protein Science, Munich (CIPSM), Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747, Garching, Germany.
authors.forename: Megan H
authors.initials: MH
authors.lastname: Wright
authors.affiliation: Center for Integrated Protein Science, Munich (CIPSM), Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747, Garching, Germany. stephan.sieber@tum.de.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Sieber
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry; D001686:Biological Phenomena; D001688:Biological Products / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000480:Alkynes; D001386:Azides; D001688:Biological Products; D001710:Biotin
keywords: chemical biology; natural products; photoprobes; synthetic functionalization; target identification