title: The dock-and-lock method combines recombinant engineering with site-specific covalent conjugation to generate multifunctional structures.
abstract: Advances in recombinant protein technology have facilitated the production of increasingly complex fusion proteins with multivalent, multifunctional designs for use in various in vitro and in vivo applications. In addition, traditional chemical conjugation remains a primary choice for linking proteins with polyethylene glycol (PEG), biotin, fluorescent markers, drugs, and others. More recently, site-specific conjugation of two or more interactive modules has emerged as a valid approach to expand the existing repertoires produced by either recombinant engineering or chemical conjugation alone, thus advancing the range of potential applications. Five such methods, each involving a specific binding event, are highlighted in this review, with a particular focus on the Dock-and-Lock (DNL) method, which exploits the natural interaction between the dimerization and docking domain (DDD) of cAMP-dependent protein kinase (PKA) and the anchoring domain (AD) of A-kinase anchoring proteins (AKAP). The various enablements of DNL to date include trivalent, tetravalent, pentavalent, and hexavalent antibodies of monospecificity or bispecificity; immnocytokines comprising multiple copies of interferon-alpha (IFNα); and site-specific PEGylation. These achievements attest to the power of the DNL platform technology to develop novel therapeutic and diagnostic agents from both proteins and nonproteins for unmet medical needs.
authors.affiliation: IBC Pharmaceuticals, Inc., Morris Plains, New Jersey, USA. Erossi@immunomedics.com
authors.forename: Edmund A
authors.initials: EA
authors.lastname: Rossi
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
mesh_terms: D001665:Binding Sites; D011092:Polyethylene Glycols / Q000737:chemistry; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D011994:Recombinant Proteins; D011092:Polyethylene Glycols