PMID- 22168393
OWN - NLM
STAT- MEDLINE
DCOM- 20120727
LR  - 20181201
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 23
IP  - 3
DP  - 2012 Mar 21
TI  - The dock-and-lock method combines recombinant engineering with site-specific 
      covalent conjugation to generate multifunctional structures.
PG  - 309-23
LID - 10.1021/bc2004999 [doi]
AB  - 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 (IFNalpha); 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.
FAU - Rossi, Edmund A
AU  - Rossi EA
AD  - IBC Pharmaceuticals, Inc., Morris Plains, New Jersey, USA. 
      Erossi@immunomedics.com
FAU - Goldenberg, David M
AU  - Goldenberg DM
FAU - Chang, Chien-Hsing
AU  - Chang CH
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20120110
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Binding Sites
MH  - Polyethylene Glycols/chemistry
MH  - *Protein Engineering
MH  - Recombinant Proteins/chemistry
EDAT- 2011/12/16 06:00
MHDA- 2012/07/28 06:00
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/07/28 06:00 [medline]
AID - 10.1021/bc2004999 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2012 Mar 21;23(3):309-23. doi: 10.1021/bc2004999. Epub 2012 Jan 
      10.