Jul, 2001
Significance of substrate hydrophobicity for recognition by an oligopeptide transporter (PEPT1)
BIOCONJUGATE CHEMISTRY
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- Volume
- 12
- Number
- 4
- First page
- 485
- Last page
- 492
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1021/bc000135u
- Publisher
- AMER CHEMICAL SOC
Our previous paper [(1999) Bioconjugate Chem. 10, 24-31] pointed out that hydrophobicity of substrates/inhibitors plays an important role in the recognition by an oligopeptide transporter (PEPT1) expressed in the human intestinal epithelial cell line Caco-8. To determine the significance of that hydrophobicity, we have now synthesized dipeptide analogues conjugating the E-amino group of Lys in Val-Lys with aliphatic carboxylic acids: acetic acid (C2), propanoic acid (C3), pentanoic acid (C5), hexanoic acid (C6), and decanoic acid (C10). The affinities of these conjugates were estimated by their inhibition of the accumulation rate of Gly-Sar, a well-established substrate for PEPT1. With the increase in length of the hydrocarbon chain of the conjugates, i.e., in the hydrophobicity of the conjugates, the inhibition strengthened. Dixon-Webb plot analysis of the inhibition by the C10-conjugated dipeptide showed competitive inhibition. The trans-stimulation effect of Val-Lys conjugated to C10 or C5 on the uptake of Ceftibuten was observed using rat brush border membrane vesicles. This findings showed that these conjugates are transportable substrates. These results confirmed that the hydrophobicity of substrates/inhibitor is one of the factors in the recognition by PEPT1.
- Link information
- ID information
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- DOI : 10.1021/bc000135u
- ISSN : 1043-1802
- Web of Science ID : WOS:000169981300005