Antibody fragments Diabodies

Holliger, P, Prospero, T, and Winter, G. (1993) Diabodies - small bivalent and bispecific antibody fragments. Proc. Natl Acad Sci USA 90,6444-6448... 

Holliger P, Prospero T, Winter G, Diabodies, small bivalent and biospecific antibody fragments, Proc. Natl. Acad. Sci. USA., 90 6444-6448, 1993. 

McGuinness BT, Walter G, FitzGerald K, Schuler P, Mahoney W, Duncan AR, Hoogenboom HR, Phage diabody repertoires for selection of large numbers of bispecific antibody fragments, Nat. Biotech., 14 1149-1154, 1996. 

Synthesis of the diabody was carried out by means of a modification of the method reported in Refs [4.17, 4.18] for synthesis of the ior-CEAI murine antibody scFv fragment. A non-covalent dimer association was obtained from two identical ior-CEAI scFv antibody fragments, in which VL and Vl domains were linked via a 5 amino acid residue. A hexahistidine tag at the C-terminus of the Vl domain aided protein purification. 

Li L, Olafsen T, Anderson A L, et al. (2002). Reduction of kidney uptake in radiometal labeled peptide linkers conjugated to recombinant antibody fragments. Site-specific conjugation of DOTA-peptides to a Cys-diabody. Bioconjug. Chem. 13 985-995. 

One scFv fragment coupled to the C-terminus of the Cm domain of a Fab fragment. See Schoonjans, R., Willems, A., Schoonooghe, S. et al.. Fab chains as an efficient heterodimerization scaffold for the production of recombinant bispecific and trispecific antibody derivatives, J. Immunol 165, 7050-7057, 2000. See also Diabody Tribody. 

In future, many antibody-derived molecules will be seen in many indications, in addition to single chain Fv fragments (scFv). Dimeric and tetrameric mini-antibodies, diabodies, single antibody domains, Fv fragments fused to toxins, cytokines, antibiotics or radionuclides, protein scaffolds with hypervariable antibody domains, and related molecules such as an-ticalines will emerge to complement the toolbox of affinity-based agents and enhance their therapeutic efficacy. 

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