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Negative Cooperativity in the Molecular Recognition of Excitatory Amino‐Acid Derivatives by Synthetic Allosteric 1,1′‐Binaphthalene Receptors
Author(s) -
Lustenberger Philipp,
Welti Roger,
Diederich François
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19981216)81:12<2190::aid-hlca2190>3.0.co;2-1
Subject(s) - chemistry , cooperativity , allosteric regulation , stereochemistry , cooperative binding , moiety , amino acid , crystallography , binding site , receptor , biochemistry
The optically active allosteric receptors (−)‐( R , R )‐ 3 and (+)‐( R , R )‐ 4 were synthesized for the molecular recognition of the N ‐(benzyloxy)carbonyl ( N ‐Cbz)‐protected excitatory amino acids aspartic acid (Asp, 1 ) and glutamic acid (Glu, 2 ). These macrocyclic structures consist of two 1,1′‐binaphthalene moieties connected by two but‐2‐yne‐1,4‐diyl (for (−)‐( R , R )‐ 3 ) or p ‐xylylene (for (+)‐( R , R )‐ 4 ) bridges between the O‐atoms in the minor grooves. Each 1,1′‐binaphthalene moiety contains two 2‐acetamidopyridin‐6‐yl (CONH(py)) H‐bonding sites in the major groove to bind excitatory amino‐acid derivatives via two COOH█bk█⋅⋅⋅█ek█CONH(py) H‐bonding arrays and additional secondary electrostatic interactions. The formation of stable complexes with 1 : 2 host‐guest stoichiometry was proven by the evaluation of fluorescence binding titrations using a multiple‐wavelength nonlinear least‐squares curve‐fitting procedure, Job plot analysis, and solubilization experiments. Complexation of the first excitatory amino‐acid guest at binding site 1 reduces the affinity for the second guest at binding site 2. As measures for the negative cooperativity between the two sites, the ratios of the association constants for the first and second binding events, { K a (1 : 1)/ K a (1 : 2)} corr. (corrected for the statistical preference of the 1 : 1 complex formation), were found to adopt values between 1.4 and 2.4, and the Hill coefficients n H varied between 0.49 and 0.59.