Mimotopes

Folgori, A., Taft, R., Meola, A., Felici, F., Galfre, G., Cortese, R., Monaci, P., and Nicosia, A. (1994). A general strategy to identify mimotopes of pathological antigens using only random peptide libraries and human sera. EMBO J. 13, 2236-2243. 

El-Kasmi, K. C., Deroo, S., Theisen, D. M., Brons, N. H. C. and Muller, C. P. (1999), Crossreactivity of mimotopes and peptide homologues of a sequential epitope with a monoclonal antibody does not predict crossreactive immunogenicity , Vaccine, 18, 284-290. 

J. G. Joyce, I. J. Krauss, H. C. Song, D. W. Opalka, K. M. Grimm, D. D. Nahas, M. T. Esser, R. Hrin, M. Feng, V. Y. Dudkin, M. Chastain, J. W. Shiver, et al., An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions, Proc. Natl. Acad. Sci. USA, 105 (2008) 15684-15689. 

Table 2 Mimotopes, or carbohydrate-mimetic peptides capable of inducing anti-...

Molecular modeling has been applied to investigate peptide mimicry of the Lewis Y tetrasaccharide. The peptide APWLYGPA, first reported by Hoess et al. [12], and shown to be a mimotope [54], binds to the monoclonal anti-Lewis Y antibody B3. A model of the antibody was constructed com-... 

Arnon, R., Tarrab-Hazdai, R. and Steward, M. (2000) A mimotope peptide-based vaccine against Schistosoma mansoni synthesis and characterization. Immunology 101, 555-562. 

Fig. 1. Graft polymer devices manufactured and sold by Mimotopes Pty Ltd for solid-phase synthesis.

Mimotopes has been involved in the development, use, and commercialization of radiation-grafted polymer surfaces for multiple parallel synthesis since the late 1980s.10-12 Although other workers have reported the use of radiation-graft polymers in solid-phase synthesis,13,14 as far as we are aware, the graft polymer devices manufactured and sold by Mimotopes (SynPhase Crowns, SynPhase Lanterns) are the only current commercial products of this type. These products are presented in Fig. 1. The SynPhase Lanterns are the current design for small molecule synthesis. The initial... 

In the mid to late 1990s, Mimotopes was producing rigid injection molded polypropylene devices that were surface grafted with either a hydrophilic copolymer of methacrylic acid/dimethyl acrylamide or the relatively hydrophobic polystyrene.12 The polymer was then suitably deriva-tized to allow the incorporation of a linker system. In contrast to the various commercial resins available at the time, the Crown was a macroscopic, quantized solid phase. As shown in Fig. 2, the Crowns were typically fitted to a polypropylene stem, which in turn could be fitted into a... 

Benzodiazepines were the first class of heterocyclic compounds to be synthesized on the SynPhase surface. In 1994, Ellman and co-workers24 reported a 192 member library of structurally diverse 1,4-benzodiazepines. These compounds were prepared on Mimotopes pins that were grafted with polyacrylic acid, the surface originally used for antibody epitope elucidation.10 Ellman and co-workers25 subsequently synthesized a 1680-member 1,4-benzodiazepine library on SynPhase Crowns that were grafted with a methacrylic acid/dimethylacrylamide copolymer, one of the first SynPhase surfaces designed for solid-phase synthesis. The synthesis was performed on a preformed linker-template system in order to avoid low aminobenzophenone incorporation in this case the HMP acid-labile linker... 

Mimotopes SynPhase Application Note SCN005, www.synphase.com... 

A system based on grafted polymer synthetic objects (lanterns) is available from Mimotopes Pyt. Ltd.12 The system is composed of the synthetic objects (lanterns), RF-Tags (Transtems), software to track the synthesis (TranSort), and a cleavage system. Additional systems that are not commercially available have been reported. Workers at Aventis have developed a highly automated system based on the Mimotope lanterns.13 Recently workers at Millenium Pharmaceuticals reported the St AC system (Stratified Adressable System), a three-dimensional spatial array that allows discrete compounds to be synthesized using the same efficiency as the directed sorting approach.14... 

The support units used in the string synthesis were Chiron Mimotopes Crowns shown in Fig. 1. They were used together with different color stems, also purchased from Chiron Mimotopes. Spatially ordered groups are formed with the crowns (Fig. 1A) by stringing them together with a thread. The stems serve to string the crowns together and to facilitate redistribution. The stems were modified as shown in Fig. 1. 

Fig. 1. Chiron Mimotopes Crowns. (A) Crown (B) stem (C) carved stem with hole (D) support unit (E) full-length stem labeling the head of the string. The scratches represent the string number (F) half stem that marks the tail of the string (G) Mimotopes SynPhase Lantern with stem.

The synthesis was carried out using 125 Chiron Mimotopes Crowns (capacity 5.3 pmol each) derivatized with an Fmoc -Rink amide linker. The procedure was started with the formation of five strings by threading 25 crown units on Berkley Fire Line fishing line. Five Fmoc-protected amino acids were used in each coupling position as demonstrated in the flow diagram of the synthesis (Fig. 11). 

An alternative solution is to produce a solid-phase particle that yields micromolar amount of product. Mimotopes Pty. Ltd. has developed and commercialized the SynPhase Crown and later Lanterns, a rigid polypropylene mold with a grafted layer of polystyrene. The solid-phase synthesis takes place on the derivatized graft.11... 

Andrew M. Bray (3), Mimotopes Pty Ltd., 11 Duerdin Street, Clayton, Victoria, 3168, Australia... 

Hou, Y. and Gu, X. X. (2003) Development of peptide mimotopes of lipo-oligosaccharide from nontypeable Haemophilus influenzae as vaccine candidates. J. Immunol. 170,4373-4379. 

Reineke, U Ivascu, C Schlief, M., et al. (2002) Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences../. Immunol. Methods 267, 37-51. 

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