Structure control within poly(amidoamine) dendrimers: size, shape and regio-chemical mimicry of globular proteins

Abstract

This work describes the syntheses of a new poly(amidoamine) (PAMAM) dendrimer family possessing a disulfide function (cystamine) in its core. Traditional redox-chemistry associated with the disulfide core in these dendrimer structures, provides a versatile strategy for designing unique sizes, shapes and controlling the regio-disposition of chemical groups on the surface of these dendrimers. Various single site, sulfhydryl functionalized dendron reactants may be generated in situ, under standard reducing conditions (i.e. dithiothreitol (DTT)). Facile control of size, shape and chemical functionality placement involves covalent hybridization of these single point, sulfhydryl reactive dendron components. This is accomplished by re-oxidation in the presence of air, to yield generation/surface chemistry differentiated cross-over products which may be isolated by preparative thin layer or column chromatography. Differentiated cystamine core dendrimers derived from combination and permutation of lower generation (i.e. Gen.=0–3) sulfhydryl functionalized dendrons possessing amino, hydroxyl, acetamido or dansyl surface groups, were synthesized and isolated. They were characterized by a variety of methods including; 13C NMR, capillary electrophoresis (CE), gel electrophoresis (PAGE), thin layer chromatography (TLC) and electrospray (ES) or matrix assisted laser desorption ionization (MALDI-TOF) mass spectrometry. This general strategy has broad implications for the systematic size, shape and regio-chemical control of a wide range of dendritic nanostructures, many of which may be designed to mimic the sizes, shapes and regio specific chemo-domains observed for globular proteins.