Antibody mimic

Vlatakis, G Andersson, LI Muller, R Mosbach, K, Drug Assay using Antibody Mimics Made by Molecnlar Imprinting, Nature 361, 645, 1993. 

Table 7 Chorismate mutase and a catalytic antibody mimic."...

Table 8 Another catalytic antibody mimic of chorismate mutase."...

Vlatakis G, Andersson LI, Muller R, Mosbach K. Drug assay using antibody mimics made by molecular imprinting. Nature 1993 361 645-647. 

Similarly to their natural counterparts (enzymes, antibodies, and hormone receptors), MIPs have found numerous applications in various areas. They have been used as antibody mimics in immunoassays and sensors and biochips as affinity separation materials and for chemical and bioanalysis, for directed synthesis and enzyme-like catalysis, and for biomedical applications. Concerning their commercialization, there has been great progress during the past decade, in particular in the... 

Shea and colleagues [109-111] added an exciting contribution to this field They created molecular imprints for the peptide melittin, the main component of bee venom, in polymer nanoparticles, resulting in artificial antibody mimics that can be used for the in vivo capture and neutralization of melittin. Melittin is a peptide comprising 26 amino acids which is toxic because of its cytolytic activity. Shea and colleagues strategy was to synthesize cross-linked, acrylamide-based MIP nanoparticles by a process based on precipitation polymerization using a small amount of surfactant. To maximize the specificity and the affinity for melittin, a number of hydrophilic monomers were screened for complementarity with the template. The imprinted nanoparticles were able to bind selectively the peptide with an apparent dissociation constant of Ax>app > 1 nM [109]. 

Molecularly imprinted polymers (MIPs) have been used in many different applications, such as affinity separation matrices [6, 7], antibody mimics in immunoassays [8-11], recognition elements in biosensors [12-16], selective... 

Ansell RA (2005) Applications of MIPs as antibody mimics in immunoassays. In Yan M, Ramstrom O (eds) Molecularly imprinted polymers science and technology. Marcel Dekker, New York... 

A monoclonal antibody which reacts with an epitope within the M domain has recently been used to check whether it influences the receptor s DNA binding properties [65]. The immune complex with wild-type receptors was indeed found to chromatograph on DNA-cellulose similar to nt1 mutant receptors or the chymo-trypsin-degraded wild-type. Reaction with the antibody mimics the removal of the M domain which suggests that biochemical modifications of the M domain could... 

Molecular imprinting is a technique in which the shape of a template molecule (analyte) is imprinted in a polymer, e.g. described by Kriz et al. (1997), Reid et al. (1998), Yano (1999), Yan (2002). The imprinted polymer can be used as an antibody mimic for an immunoassay. 

Yan M (2002) Molecular Imprinted Polymers as Antibody Mimics Applications in Immunoassays and Recent Developments. Journal of Clinical Ligand Assay 25(2) 234-236... 

The use of antibody catalysis is attracting attention, especially because antibody catalysis is as yet the only approach available which uses an ab initio method for the development of new catalysts for example, the antibody mimics the shape of a transition state of the substrates, thus enhancing catalytic reaction rates. Economic application may lie far in the future, however. There is no such approach available in classical metal (complex) catalysis, however, and we have to rely on the development of known catalytic reactions and the development of accidentally discovered leads. 

An example of this approach is demonstrated in an antibody mimic of the enzyme ferrochetalase (39). Ferrochelatase catalyzes the insertion of Fe + into protoporphyrin IX (3) as the last step in the heme biosynthetic pathway (40). Interestingly, N-alkylporphyrins are known to be potent inhibitors of this enzyme, because alkylation at one pyrrole lutrogen distorts the planarity of the porphyrin macrocycle (41). This finding was used in the design of hapten 4 to catalyze the incorporation of metal ions into mesoporphyrin IX (5) by eliciting an antibody that binds the substrate in a ring-strained conformation. 

Molecularly imprinted polymers have come to be recognised as antibody mimics since Mosbach and co-workers demonstrated the use of imprinted polymers for the sorbent assay of drugs [1], Not only in applications, but also in preparation principle, imprinted polymers can be regarded as antibody mimics the synthesis proceeds in a tailor-made fashion and the resultant polymers show specific binding for a given guest molecule. Also, imprinted polymers have many characteristic features as synthetic antibody mimics that contrast with natural antibodies. 

USE OF MOLECULARLY IMPRINTED POLYMERS (MIPs) AS ANTIBODY MIMICS... 

The construction of "a calixarene with four peptide loops" serves two functions in this article. It serves as a simplified substitute for an antibody, though we doubt that the intent of the authors is the design of potential therapeutic agents. More important, the calixarene serves to test the theory of antibody function sketched in the preceding discussion Is this really the way that antibodies work The authors note that earlier attempts to mimic antibodies have been unsuccessful, and they propose the alternative strategy, which is the heart of the article The search for antibody mimics has not yet yielded compact and robust frameworks that reproduce the essential features of the CDRs. Our strategy is to use a macrocyclic scaffold to which multiple peptide loops in stable hairpin-turn conformations can be attached (p. 2681). 

In this paper we report the synthesis of an antibody mimic based on calix[4]arene linked to four constrained peptide loops.. . . Calix[4]arene was chosen as the core scaffold, as it is readily available and can be locked into the semirigid cone conformation by alkylation of the phenol groups. This results in a projection of the para-substituents onto the same side of the ring to form a potential binding domain. (p. 2681)... 

Once the antibody mimic has been assembled, it can be tested to see whether it in fact behaves like an antibody, a test which, if successful, in turn provides evidence supporting the theory of the action of antibodies invoked by Hamuro et al. Note the usefully—as opposed to viciously—circular reasoning here (Hoffmann, 1988) the antibody mimic correctly mimics an antibody if it behaves like an antibody but how an antibody behaves is still a postulate, which stipulates what counts as the correctness of the antibody mimic s mimicry. To see if the antibody mimic—the base scaffold of calixarene with four peptide loops—will bind with and impair the function of a protein (the essence of what an antibody does), Hamuro et al. chose the protein... 

Note that the antibody mimic is referred to by means of the diagram 3. In a sense this is because the diagram is a shorthand, but its perspicuity is not trivial or accidental as a picture that can be taken in at a glance, it offers schematically the whole configuration of the molecule in space. Its visual unity stands for, and does not misrepresent, the unity of the molecule s existence. 

Figure 13.3 is another measurement, with the concentrations measured on the vertical axis, the time on the horizontal it displays the outcome of an experiment on the kinetics of ascorbate reduction by cytochrome c, which supports the claim that the antibody mimic does impair the function of the protein, in this case its ability to react with ascorbate. 

Hamuro, Yoshimoto, Hamilton, Andrew D., Calama, Mercedes Crego, Park, Hyung Soon. 1997., "A Calixarene with Four Peptide Loops An Antibody Mimic for Recognition of Protein Surfaces." Angewandte Chemie, International English Edition, 36(23) 2680-2683. 

Lipovsek, D., Lippow, S. M., Hackel, B. J., Gregson, M. W., Cheng, P., Kapila, A. and Wittrup, K D. (2007) Evolution of an interloop disulfide bond in high-affinity antibody mimics based on fibronectin type III domain and selected by yeast surface display molecular convergence with single-domain camelid and shark antibodies. J Mol Biol 368, 1024-1041... 

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