Solid-phase dendrimer synthesis

✍ Scribed by Neil J. Wells; Andrea Basso; Mark Bradley

• Publisher: Wiley (John Wiley & Sons)
• Year: 1998
• Tongue: English
• Weight: 262 KB
• Volume: 47
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/(sici)1097-0282(1998)47:5<381::aid-bip5>3.0.co;2-f

✦ Synopsis

Dendrimers are highly ordered, hyperbranched polymers with potential for a whole range of chemical applications. Solution-phase synthesis of dendrimers is often challenging, requiring long reaction times and nontrivial purification; solid-phase methodology, on the other hand, enables reactions to be driven to completion by using a large excess of reagents with trivial purification. In this paper we show that polyamidoamine dendrimers may be synthesized conveniently and efficiently on a solid support, and that these molecules are of good homogeneity as characterized by 1 H-and 13 C-nmr and electrospray mass spectrometry. These solid-phase dendrimers were used as a bead loading amplification tool in the synthesis of a hexapeptide library (Xaa-Gly-Gly-Phe-Leu-Lys) to allow single bead analysis as well as allowing the efficient synthesis of two dendrimer conjugates (Leu-enkephalin-Lys and Chlorambucil). This demonstrated that peptides and small drug molecules can be grown directly onto the dendrimer or onto a linker attached to the dendrimer periphery, enhancing general dendrimer utility.