A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.
Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model.We synthesized novel retinoid analogues and deriva...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2848850?pdf=render |
| _version_ | 1818137702892044288 |
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| author | Bhaskar C Das Kellie McCartin Ting-Chun Liu Randall T Peterson Todd Evans |
| author_facet | Bhaskar C Das Kellie McCartin Ting-Chun Liu Randall T Peterson Todd Evans |
| author_sort | Bhaskar C Das |
| collection | DOAJ |
| description | Retinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model.We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested.Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity. |
| first_indexed | 2024-12-11T10:00:30Z |
| format | Article |
| id | doaj.art-55adfa2f4a4f47b4a4cef17c2a5cec91 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T10:00:30Z |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-55adfa2f4a4f47b4a4cef17c2a5cec912022-12-22T01:12:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1000410.1371/journal.pone.0010004A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity.Bhaskar C DasKellie McCartinTing-Chun LiuRandall T PetersonTodd EvansRetinoids regulate key developmental pathways throughout life, and have potential uses for differentiation therapy. It should be possible to identify novel retinoids by coupling new chemical reactions with screens using the zebrafish embryonic model.We synthesized novel retinoid analogues and derivatives by amide coupling, obtaining 80-92% yields. A small library of these compounds was screened for bioactivity in living zebrafish embryos. We found that several structurally related compounds significantly affect development. Distinct phenotypes are generated depending on time of exposure, and we characterize one compound (BT10) that produces specific cardiovascular defects when added 1 day post fertilization. When compared to retinoic acid (ATRA), BT10 shows similar but not identical changes in the expression pattern of embryonic genes that are known targets of the retinoid pathway. Reporter assays determined that BT10 interacts with all three RAR receptor sub-types, but has no activity for RXR receptors, at all concentrations tested.Our screen has identified a novel retinoid with specificity for retinoid receptors. This lead compound may be useful for manipulating components of retinoid signaling networks, and may be further derivatized for enhanced activity.http://europepmc.org/articles/PMC2848850?pdf=render |
| spellingShingle | Bhaskar C Das Kellie McCartin Ting-Chun Liu Randall T Peterson Todd Evans A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. PLoS ONE |
| title | A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. |
| title_full | A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. |
| title_fullStr | A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. |
| title_full_unstemmed | A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. |
| title_short | A forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity. |
| title_sort | forward chemical screen in zebrafish identifies a retinoic acid derivative with receptor specificity |
| url | http://europepmc.org/articles/PMC2848850?pdf=render |
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