Protein-based antagonists

All the protein-based potential therapeutics discussed above fail to meet any of these criteria. Low molecular mass antagonists of IL-5 or its receptor may prove of most use. A number of research teams are screening for such substances. The development strategies pursued include ... 

In particular, a molecularly imprint-based CEC system was compared with an immobilised protein-based system and a cyclodextrin-based system for the enantiomer separation of )8-adrenergic antagonists. It was shown that the MIP-based system could separate all the analytes tested without any change in the experimental conditions (i.e electrolyte composition). This was not possible using the other systems. The chromatographic efficiency, however, was superior for the cyclodextrin-based system. The poor efficiency is a rather discouraging, yet common, feature of molecular imprint-based separation systems. Also, the protein-based systems showed poor efficiency in this study, but optimised conditions can improve this [72,73]. Nevertheless, the MIP-based and protein-based systems showed good selectivity. 

Ernst, J. T., Kutzki, O., Debnath, A. K, Jiang, S., Lu, H., and Hamilton, A. D. (2002) Design of a protein surface antagonist based on alpha-helix mimicry Inhibition of gp41 assembly and viral fusion. Angew. Chem. Lnt. Ed. Engl. 41, 278-281. 

Cohen F, Koehler MFT, Beigeron P et al (2010) Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres. Bioorg Med Chem Lett 20 2229-2233... 

The existence of further alternative transcripts of MOP was postulated by the observation that in knockout mice with disrupted exon 1, heroin but not morphine was still analgesically active. Based on earlier observations that the antagonist naloxazone blocked morphine-induced antinociception but not morphine-induced respiratory depression, a subdivision of the MOP in pi and p2 was proposed. However, no discrete mRNA for each of these MOP subtypes has been found. It is, however, possible that subtypes of MOPs result from heterodimerization with other opioid receptors or by interaction with other proteins. 

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