Dendrimers as carrier protein mimetics for IgE antibody recognition. Synthesis and characterization of densely penicilloylated dendrimers.
The synthesis of benzylpenicilloyl-containing dendrimers has been achieved by a convenient procedure involving quantitative functionalization of the terminal amino groups of the three Starbust PAMAM generations used (G(n); n = 0, 1, 2). All these densely penicilloylated dendrimers (G(n)P) exhibit similar, simple NMR spectroscopic data suggesting highly symmetric structures and a monodisperse nature, and the results obtained from MALDI-TOF-MS demonstrate their exact chemical composition. The use of PAMAM dendrimers has allowed us to synthesize, for the first time, carrier benzylpenicilloyl conjugates (G(n)P) of precisely defined chemical structure. The attempts to synthesize G(2)P show that forced experimental conditions are not always useful for the functionalization of the dendrimer, especially in introducing bulky groups. The initial results with sera from patients with different RAST levels were positive and thus suggestive that inhibition occurs, so recognition exists; we can therefore conclude that the hapten-carrier (dendrimer) conjugates studied mimic recognition with natural hapten-carrier (protein) conjugates.
Sánchez-Sancho
Francisco
F
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, E-29071, Spain.
Pérez-Inestrosa
Ezequiel
E
Suau
Rafael
R
Mayorga
Cristobalina
C
Torres
María J
MJ
Blanca
Miguel
M
D044482:Benzeneacetamides; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D002352:Carrier Proteins / Q000276:immunology*; D050091:Dendrimers; D006241:Haptens / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D010400:Penicillin G / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D011852:Radioallergosorbent Test; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D044482:Benzeneacetamides; D001672:Biocompatible Materials; D002352:Carrier Proteins; D050091:Dendrimers; D006241:Haptens; C104700:PAMAM Starburst; D010718:Phosphatidylserines; D011073:Polyamines; C015026:benzylpenicilloyl G; D007073:Immunoglobulin E; D010400:Penicillin G