TY - JOUR
T1 - Utilization of Photoaffinity Labeling to Investigate Binding of Microtubule Stabilizing Agents to P-Glycoprotein and β-Tubulin
AU - Huang Yang, Chia Ping
AU - Horwitz, Susan Band
AU - McDaid, Hayley M.
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/3/25
Y1 - 2022/3/25
N2 - Photoaffinity labeling approaches have historically been used in pharmacology to identify molecular targets. This methodology has played a pivotal role in identifying drug-binding domains and searching for novel compounds that may interact at these domains. In this review we focus on studies of microtubule stabilizing agents of natural product origin, specifically taxol (paclitaxel). Taxol and other microtubule interacting agents bind to both P-glycoprotein (ABCB1), a drug efflux pump that reduces intracellular drug accumulation, and the tubulin/microtubule system. Both binding relationships modulate drug efficacy and are of immense interest to basic and translational scientists, primarily because of their association with drug resistance for this class of molecules. We present this body of work and acknowledge its value as fundamental to understanding the mechanisms of taxol and elucidation of the taxol pharmacophore. Furthermore, we highlight the ability to multiplex photoaffinity approaches with other technologies to further enhance our understanding of pharmacologic interactions at an atomic level. Thus, photoaffinity approaches offer a relatively inexpensive and robust technique that will continue to play an important role in drug discovery for the foreseeable future.
AB - Photoaffinity labeling approaches have historically been used in pharmacology to identify molecular targets. This methodology has played a pivotal role in identifying drug-binding domains and searching for novel compounds that may interact at these domains. In this review we focus on studies of microtubule stabilizing agents of natural product origin, specifically taxol (paclitaxel). Taxol and other microtubule interacting agents bind to both P-glycoprotein (ABCB1), a drug efflux pump that reduces intracellular drug accumulation, and the tubulin/microtubule system. Both binding relationships modulate drug efficacy and are of immense interest to basic and translational scientists, primarily because of their association with drug resistance for this class of molecules. We present this body of work and acknowledge its value as fundamental to understanding the mechanisms of taxol and elucidation of the taxol pharmacophore. Furthermore, we highlight the ability to multiplex photoaffinity approaches with other technologies to further enhance our understanding of pharmacologic interactions at an atomic level. Thus, photoaffinity approaches offer a relatively inexpensive and robust technique that will continue to play an important role in drug discovery for the foreseeable future.
UR - http://www.scopus.com/inward/record.url?scp=85126322717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126322717&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.2c00106
DO - 10.1021/acs.jnatprod.2c00106
M3 - Review article
C2 - 35240035
AN - SCOPUS:85126322717
SN - 0163-3864
VL - 85
SP - 720
EP - 728
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 3
ER -