Bioorganic & Medicinal Chemistry Letters 2011-07-01

The geranyl-modified tryptophan residue is crucial for ComXRO-E-2 pheromone biological activity.

Fumitada Tsuji, Ko Kobayashi, Masahiro Okada, Hisao Yamaguchi, Makoto Ojika, Youji Sakagami, Fumitada Tsuji, Ko Kobayashi, Masahiro Okada, Hisao Yamaguchi, Makoto Ojika, Youji Sakagami, Fumitada Tsuji, Ko Kobayashi, Masahiro Okada, Hisao Yamaguchi, Makoto Ojika, Youji Sakagami

Index: Bioorg. Med. Chem. Lett. 21(13) , 4041-4, (2011)

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Abstract

The ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in gram-positive bacteria, Bacillus. We have reported the structure of the ComX(RO-E-2) pheromone, which is produced by the RO-E-2 strain of Bacillus subtilis. ComX(RO-E-2) analogs with substituted amino acids and isoprenoid modified tryptophan residues (e.g., prenyl, geranyl, and farnesyl), were synthesized and examined for biological activity. These results indicate that Phe-Trp(∗)(Ger)-NH(2) is the minimum pharmacophore of the ComX(RO-E-2) pheromone. Furthermore, the length of the isoprenoid moiety (i.e., modification style), and the presence of double bonds, are crucial for biological activity. The modification style of the ComX pheromone is more important than the peptide sequence with respect to biological activity.Copyright © 2011 Elsevier Ltd. All rights reserved.