Near native binding of a fluorescent serotonin conjugate to serotonin type 3 receptors

Bioorg Med Chem Lett. 2013 Feb 1;23(3):773-5. doi: 10.1016/j.bmcl.2012.11.082. Epub 2012 Dec 1.

Abstract

Described is the synthesis of 5-hydroxytryptamine-tetramethylrhodamine (5HT*); an indole nitrogen linked fluorescent conjugate of serotonin. Through a series fluorescence quenching experiments and experiments in the presence of a known competitive antagonist (Granisetron), it was shown that 5HT* specifically binds to purified homo-pentameric type-3 human serotonin receptors (5HT(3A)). The measured dissociation constant and Hill coefficient are K(d) = 83 ± 3 nM and n = 3.1 ± 0.3, respectively which is indicative of multi-ligand binding and cooperativity similar to that of unconjugated serotonin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Fluorescence
  • Humans
  • Protein Binding
  • Receptors, Serotonin, 5-HT3 / chemistry*
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Rhodamines / chemical synthesis*
  • Rhodamines / chemistry
  • Rhodamines / metabolism
  • Serotonin / analogs & derivatives*
  • Serotonin / chemical synthesis
  • Serotonin / chemistry
  • Serotonin / metabolism

Substances

  • 5-hydroxytryptamine-tetramethylrhodamine
  • Receptors, Serotonin, 5-HT3
  • Rhodamines
  • Serotonin