title: Probing an artificial polypeptide receptor library using a series of novel histamine H3 receptor ligands.
abstract: An artificial polypeptide receptor (APR) library was created by using the self-organization of N-lipidated peptides attached to cellulose via m-aminophenylamino-1,3,5-triazine. The response of the library was probed using a series of novel H3 receptor ligands. Since no guidelines on how to design an APRs selective vs certain receptor types exist, a diverse set of amino acids (Ala, Trp, Pro, Glu, His, Lys and Ser) were used and coupled with one of three gating fatty acids (palmitic, ricinoleic or capric). A competitive adsorption-desorption of an appropriate reporter dye was used for the indirect visualization of the interactions of guests with particular receptors. The resulted library response to individual inhibitors was then arranged in a matrix, preprocessed and analyzed using the principal component analysis (PCA) and partial least squares (PLS) method. The most important conclusion obtained from the PCA analysis is that the library differentiates the probed compounds according to the lipophilicity of the gating unit. The PC3 with a dominant absolute contribution of the receptors containing Glu allowed for the best separation of the ligands with respect to their activity. This conclusion is in agreement with the fact that Glu 206 is a genuine ligand counterpart in the natural histamine receptor.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bak
authors.forename: Michal
authors.initials: M
authors.lastname: Daszykowski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Kaminski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kiec-Kononowicz
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuder
authors.forename: Justyna
authors.initials: J
authors.lastname: Fraczyk
authors.forename: Beata
authors.initials: B
authors.lastname: Kolesinska
authors.forename: Patrycja
authors.initials: P
authors.lastname: Ciosek
authors.affiliation: Institute of Chemistry, University of Silesia, 40-006 Katowice, Poland. polanski@us.edu.pl.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Polanski
mesh_terms: D055808:Drug Discovery; D006633:Histamine Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*
chemical_list: D006633:Histamine Antagonists; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D018100:Receptors, Histamine H3