title: Enabling ScFvs as multi-drug carriers: a dendritic approach.
abstract: To enable scFvs as multi-drug carriers, we designed and synthesized dendritic linker molecules bearing up to nine chlorambucil residues at the branch ends. A maleimide group was used at the focal point of the dendron for easy linkage to the scFv. Originally designed molecules showed poor water solubility. To address this problem, a lysine residue with an unprotected carboxylic acid group was inserted into the dendron branches. The new molecules showed excellent water solubility and are now suitable for conjugation. Such dendritic molecules will allow studies to understand the relationship between the drug/antibody ratio and the potency of the immunoconjugates. The dendritic approach could also be applied to drugs other than chlorambucil and carriers other than scFvs to greatly increase the drug/carrier ratio.
authors.affiliation: Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Chengzao
authors.initials: C
authors.lastname: Sun
authors.forename: Peter
authors.initials: P
authors.lastname: Wirsching
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D002699:Chlorambucil / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D012995:Solubility
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D002699:Chlorambucil