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One‐Armed Artificial Receptors for the Binding of Polar Tetrapeptides in Water: Probing the Substrate Selectivity of a Combinatorial Receptor Library
Author(s) -
Schmuck Carsten,
Heil Martin
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200501062
Subject(s) - tetrapeptide , chemistry , selectivity , substrate (aquarium) , receptor , peptide , stereochemistry , combinatorial chemistry , biochemistry , biology , ecology , catalysis
We have recently developed a new class of one‐armed artificial receptors 1 for the binding of the polar tetrapeptide N ‐Ac‐ D ‐Glu‐ L ‐Lys‐ D ‐Ala‐ D ‐Ala‐OH (EKAA) 2 in water using a combined combinatorial and statistical approach. We have now further probed the substrate selectivity of this receptor library 1 by screening a second tetrapeptide substrate ( 3 ) with the inverse sequence N ‐Ac‐ D ‐Ala‐ D ‐Ala‐ L ‐Lys‐ D ‐Glu‐OH (AAKE). This “inverse” substrate is also efficiently bound by our receptors, with K ass ≈6000 m −1 for the best receptors, as determined both by a quantitative on‐bead binding assay and by UV and fluorescence titration studies in free solution. Hence, the inverse tetrapeptide 3 is in general bound two to three times less efficiently than the “normal” peptide 2 ( K ass ≈17 000 m −1 ), even though the complexation mainly involves long‐range electrostatic interactions and both the receptor and substrate are rather flexible. Molecular modeling and ab initio calculations have been used to rationalize the observed substrate selectivity and to analyze the various binding interactions within the complex.