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Identification of Novel Compounds for Human Bitter Taste Receptors

Authors

  • Mingfei Ji,

    1. Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
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    • The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint first authors.
  • Xubo Su,

    1. Department of Pathophysiology and Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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    • The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint first authors.
  • Xiaohong Su,

    1. Department of Pharmacology, Dalian Medical University, Dalian, China
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    • The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint first authors.
  • Yingyi Chen,

    1. Department of Pathophysiology and Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
    2. Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Wenkang Huang,

    1. Department of Pathophysiology and Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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  • Jian Zhang,

    1. Department of Pathophysiology and Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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  • Zhaobin Gao,

    1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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  • Chuangang Li,

    Corresponding author
    1. Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
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  • Xuefeng Lu

    Corresponding author
    1. Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract

The finely tuned bitter taste sensing in humans is orchestrated by a group of 25 bitter taste receptors (TAS2Rs), which belong to the G-protein-coupled receptor superfamily. TAS2Rs are expressed in the specialized taste bud cells of the gustatory system and perceive a plethora of bitter substances with versatile structures. To date, more than one hundred bitter ligands have been matched with their cognate receptors, but the understanding of the molecular mechanisms of TAS2Rs remains limited. Additionally, the extraoral expression of TAS2R genes was found in the gastrointestinal tract and respiratory system, which suggests other important physiological functions for TAS2Rs. To gain insight into the physiological functions of TAS2Rs, we established a heterologous expression system and characterized the response of 24 TAS2Rs against a library of potential bitter compounds. Among these bitter compounds of interest, 18 bitter compounds activated 16 TAS2Rs, representing 42 tastant–receptor pairs. We then calculated 14 descriptor properties for the 18 positive compounds. By comparison with 102 previously annotated bitter compounds in the database, we discovered common descriptor properties that may contribute to the discovery of additional bitter ligands and further expand the known molecular receptive ranges of human TAS2Rs.

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