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Tetrapeptide inhibitors of the glutamate vesicular transporter (VGLUT).
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 Sep 15; Vol. 17 (18), pp. 5125-8. Date of Electronic Publication: 2007 Jul 26. - Publication Year :
- 2007
-
Abstract
- Quinoline-2,4-dicarboxylic acids (QDCs) bearing lipophilic substituents in the 6- or 7-position were shown to be inhibitors of the glutamate vesicular transporter (VGLUT). Using the arrangement of the QDC lipophilic substituents as a template, libraries of X(1)X(2)EF and X(1)X(2)EW tetrapeptides were synthesized and tested as VGLUT inhibitors. The peptides QIEW and WNEF were found to be the most potent. Further stereochemical deconvolution of these two peptides showed dQlIdElW to be the best inhibitor (K(i)=828+/-252 microM). Modeling and overlay of the tetrapeptide inhibitors with the existing pharmacophore showed that H-bonding and lipophilic residues are important for VGLUT binding.
Details
- Language :
- English
- ISSN :
- 0960-894X
- Volume :
- 17
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 17662605
- Full Text :
- https://doi.org/10.1016/j.bmcl.2007.07.006