pgp - publications

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1. Bioorg Med Chem Lett. 2012 Mar 15;22(6):2192-4. Epub 2012 Feb 4.

Relationship between structure and P-glycoprotein inhibitory activity of dimeric
peptides related to the Dmt-Tic pharmacophore.

Ambo A, Ohkatsu H, Minamizawa M, Watanabe H, Sugawara S, Nitta K, Tsuda Y, Okada
Y, Sasaki Y.

Tohoku Pharmaceutical University, 4-1 Komatsushima 4-chome, Aoba-ku, Sendai
981-8558, Japan.

To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to
an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their
P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized,
N(α),N(ε)-[(CH(3))(2)Mle-Tic](2)Lys-NH(2) and its d-Lys analog were found to
exhibit potent P-gp inhibitory activity, twice that of verapamil, in
doxorubicin-resistant K562 cells. Structure-activity studies indicated that the
correct hydrophobicity and spacer length between two aromatic rings are important
structural elements in this series of analogs for inhibition of P-gp.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22365753 [PubMed - in process]