Artificial receptor proteins

Introduction of heme residues and different artificial receptors in protein molecules in chemical modification of structures and functions of proteins by the cofactor reconstruction method 99Ef0539. 

Imperiali B, McDonnell KA, Shogren-Knaak M (1999) Design and Construction of Novel Peptides and Proteins by Tailored Incorparation of Coenzyme Functionality. 202 1-38 Jacques VjDesreux JF(2002) New Classes of MRI Contrast Agents. 221 123-164 James TD, Shinkai S (2002) Artificial Receptors as Chemosensors for Carbohydrates. 218 159-200... 

Keywords Artificial receptors Molecularly imprinted polymers Plastic antibodies Protein imprinting Water compatible MIP Controlled/living radical polymerization... 

Aprotic solvents mimic the hydrophobic protein interior. However, a functional artificial receptor for flavin binding under physiological conditions must be able to interact with the guest even in competitive solvents. As found by spectroscopic measurements with phenothiazene-labeled cyclene, the coordinative bond between flavin and Lewis-acidic macrocyclic zinc in methanol was strong enough for this function. Stiochiometry of the complex was proved by Job s plot analysis. Redox properties of the assemblies in methanol were studied by cyclic voltammetry which showed that the binding motif allowed interception of the ECE reduction mechanism and stabilisation of a flavosemiquinone radical anion in a polar solvent. As a consequence, the flavin chromophore switched from a two-electron-one-step process to a two-step-one-electron-each by coordination. 

Takashima H, Shinkai S, Hamachi I. Ru(bpy)3-based artificial receptors towards a protein surface selective binding and efficient photoreduction of cytochrome c. J Chem Soc Chem Commun 1999 2345-6. 

Information Conversion and Amplification - Signal Transduction When an extracellular signal is recognized by a receptor on a cell membrane, the G-protein activates the enzyme inside the cell. The activation of an enzyme by external chemicals can be mimicked using a system consisting of an artificial receptor and an enzyme immobilized on an artificial lipid bilayer membrane. 

Followed by this initial success, Klibanov et al. carried out further systematic and in-depth studies in this direction using a large variety of proteins. By utilising bovine serum albumin (BSA) as the matrix forming protein, they prepared several such artificial receptors exhibiting shape-selective and enantioselective molecular recognition characteristics [12,13]. Thus, BSA imprinted with L-malic acid was... 

Hydrogen bonds also play an important role in anion binding, both in proteins [96] and in recently developed artificial receptors [97]. Systematic association measurements wifh model amides (Fig. 2.19) in chloroform show binding increments (Tab. 2.1) between a single amide group and different anions, which are approximately additive [98]. The AG values for chloride complexation increase from monodentate to bidentate to tridentate hosts (Fig. 2.19, 1-3), i.e., from 6 to 12 to 18 kj/mol, respectively. Noticeable deviation from additivity is observed if an an-... 

The affinities observed for complexes between amides and anions are remarkably parallel to those found for the interactions between such anions and carbohydrate models. The data in Tab. 2.1 show the same affinity increase in the sequence r
strong acceptor as the result of two geometrically matching hydrogen bonds with vicinal diols. The formation of two almost linear and parallel hydrogen bonds is also responsible for the efficiency of the guanidinium residue for carboxylate complexation in artificial receptors [101] as well as in proteins (cf. Chapter 6) [102]. 

A limited improvement in this context may be possible by the use of more stable proteins, e.g. from thermophilic bacteria. However, many principles demonstrated by nature could be transposed to sensor development. For example, biomimetic channel and carrier molecules could be used in conjunction with stabilized lipid membranes to prepare sensitive and selective electrochemical transducers which embodied the principle of intrinsic amplification by depolarization. The use of artificial receptor sites would probably result in a substantial reduction of the desired selectivity coefficients, but this could easily be compensated by the application of array processing for background correction. 

In contrast, other tastes including sweetness (as in sucrose, fructose, and artificial sweetener) are sensed by actually binding to specific membrane receptor proteins in taste receptor cells. The chemicals sensed as sweet bind to selective sites on a membrane receptor in a lock-and-key fashion (im-... 

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