Abstract
Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4756-4761 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 109 |
| Issue number | 13 |
| DOIs | |
| State | Published - Mar 27 2012 |
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Keywords
- Cellular imaging
- Enzyme substrates
- Fluorophores
- Microscopy
- Pharmacological agents
ASJC Scopus subject areas
- General
Cite this
Selective esterase-ester pair for targeting small molecules with cellular specificity. / Tian, Lin; Yang, Yunlei; Wysocki, Laura M.; Arnold, Alma C.; Hu, Amy; Ravichandran, Balaji; Sternson, Scott M.; Looger, Loren L.; Lavis, Luke D.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 13, 27.03.2012, p. 4756-4761.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective esterase-ester pair for targeting small molecules with cellular specificity
AU - Tian, Lin
AU - Yang, Yunlei
AU - Wysocki, Laura M.
AU - Arnold, Alma C.
AU - Hu, Amy
AU - Ravichandran, Balaji
AU - Sternson, Scott M.
AU - Looger, Loren L.
AU - Lavis, Luke D.
PY - 2012/3/27
Y1 - 2012/3/27
N2 - Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
AB - Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
KW - Cellular imaging
KW - Enzyme substrates
KW - Fluorophores
KW - Microscopy
KW - Pharmacological agents
UR - http://www.scopus.com/inward/record.url?scp=84859451109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859451109&partnerID=8YFLogxK
U2 - 10.1073/pnas.1111943109
DO - 10.1073/pnas.1111943109
M3 - Article
VL - 109
SP - 4756
EP - 4761
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 13
ER -