These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: 22-Alkyl-20-epi-1alpha,25-dihydroxyvitamin D3 compounds of superagonistic activity: syntheses, biological activities and interaction with the receptor.
    Author: Yamamoto K, Inaba Y, Yoshimoto N, Choi M, DeLuca HF, Yamada S.
    Journal: J Med Chem; 2007 Mar 08; 50(5):932-9. PubMed ID: 17298045.
    Abstract:
    We previously reported that 22R-methyl-20-epi-1,25-(OH)2D3 (3) possesses strong binding affinity for the vitamin D receptor (VDR) and shows superagonistic biological activities. To examine the effect of the length of an alkyl substituent at C(22) and to extend our compound library, we successfully synthesized 22R-ethyl-20-epi-1,25-(OH)2D3 (4) and 22R-butyl-20-epi-1,25-(OH)2D3 (5). Surprisingly, 22-ethyl analogue 4 showed stronger VDR binding affinity and transactivation potency than the superagonist of methyl analogue 3, but its calcemic activity in vivo was weaker than that of both the methyl analogue 3 and the natural hormone (1), while 22-butyl analogue 5 showed activities comparable to those of the hormone (1). A study of the docking of these new analogues to the VDR-LBD and alanine scanning mutational analysis demonstrated that 22-methyl and 22-ethyl substituents enhance the favorable hydrophobic interactions with residues lining the ligand binding pocket of the VDR, and that 22-butyl analogue 5 binds to the VDR by an induced fit mechanism.
    [Abstract] [Full Text] [Related] [New Search]