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Design, Synthesis, and Biological Application of Novel Photoaffinity Probes of Dihydropyridine Derivatives, BAY R3401.

ABSTRACT: To explore the molecular mechanisms of BAY R3401, four types of novel photoaffinity probes bearing different secondary tags were synthesized. Their potency for glycogenolysis was evaluated in primary human liver HL-7702 cells and HepG2 cells. Probe 2d showed the best activity in primary human liver HL-7702 cells and HepG2 cells, with IC50 values of 4.45 ?M and 28.49 ?M, respectively. Likewise, probe 5d showed IC50 values of 6.46 ?M in primary human liver HL-7702 cells and 15.29 ?M in HepG2 cells, respectively. Photoaffinity labeling experiments were also performed and protein bands larger than 170 kDa were specifically tagged by probe 2d. The results suggest that the synthesized probe 2d might be a very promising tool for the isolation of the target proteins of BAY R3401.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6652023 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Biological Application of Novel Photoaffinity Probes of Dihydropyridine Derivatives, BAY R3401.

Zhang Liying L Yan Zhiwei Z Wang Youde Y Song Chengjun C Miao Guangxin G

Molecules (Basel, Switzerland) 20190628 13

To explore the molecular mechanisms of BAY R3401, four types of novel photoaffinity probes bearing different secondary tags were synthesized. Their potency for glycogenolysis was evaluated in primary human liver HL-7702 cells and HepG2 cells. Probe 2d showed the best activity in primary human liver HL-7702 cells and HepG2 cells, with IC<sub>50</sub> values of 4.45 μM and 28.49 μM, respectively. Likewise, probe 5d showed IC<sub>50</sub> values of 6.46 μM in primary human liver HL-7702 cells and 1 ...[more]

PMID: 31261804

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