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BsAb Generation by Chemical Conjugation

Based on the advanced chemical conjugation platform we have established, Creative Biolabs is proud to offer high affinity bispecific antibodies (BsAbs) for both academic and industrial purposes. The chemical conjugation service offered by Creative Biolabs will contribute greatly to the success of your project.

Chemical Conjugation

Chemical conjugation is to develop simple and efficient approach for chemical bonding of biomolecules with other molecules. Firstly, a pre-required preceding modification of the biomolecule(s) via bifunctional reagents is necessary. These reagents are referred to linkers, which may work as spacers enhancing spatial availability of functional groups, or bring new functionalities into molecules. Usually, chemical reactivity of proteins is based on side chains of their amino acids, on their N- and C-terminal residues, or on their spatial structure. From the reactivity view point, essential side chains include β-carboxyl group of aspartic acid, ε-amino group of lysine, γ-carboxyl group of glutamic acid, as well as thiol group of cysteine. Among these side chains, the thiol of cysteine is the most powerful nucleophilic group. However, carboxyl group is the most abundant functional group in proteins. Carboxyl moieties are able to be activated as acyl esters, anhydrides, acyl azides, acylimidazoles, etc.

BsAbs from Chemical Conjugation

There are several formats of BsAbs that can be generated by chemical conjugation. Classically, one method is to conjugate two purified mAbs directly via a cross-linker to produce IgG-IgG. The other method is to generate fab fragments by enzymatic digestion and reduction of desired specific purified antibodies. Bifunctional reagents are then added to make heterodimer assembly by association of the Fab fragments. 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) coupling and o-phenylenedimaleimide (o-PDM) coupling are two methods for creating Fab' × Fab' chemically linked BsAb. DTNB acts to regenerate disulfide bonds between the two Fabs, whereas o-PDM acts to form a thioether bond between the two Fabs. In this way, the formats of F(ab’)2 and F(ab’)3 can be obtained. In bispecific molecules, the functional moieties are not just antibodies or antibody fragments but also include peptides or other elements. Antibody-peptide conjugates are such molecules, which are formed by scaffold antibody conjugated with peptides. BsAb-functionality conjugates are formed by incorporating other molecules such as PEG, siRNA, fluorophores.

The examples of bispecific molecules generated by chemical conjugation.

Figure 1. The examples of bispecific molecules generated by chemical conjugation.

The main services of developing BsAbs by chemical conjugation include:

  • Choose mAbs and antibody fragments available from us or using your own specific antibodies
  • Design an appropriate conjugation strategy (a suitable crosslinker and an optimal chemical reaction system)
  • Scale-up production, purification and characterization

We offer the following chemical crosslinkers for chemical conjugation:

  • hetero-bifunctional chemical crosslinkers: SPDP/DTT, Traut’s reagent/SMCC
  • homo-bifunctional chemical crosslinkers: DTNB, PDM
  • special linkers provide by customers

Creative Biolabs also provides other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Doppalapudi, V. R.; et al. Chemical generation of bispecific antibodies. Proceedings of the National Academy of Sciences. 2010, 107(52): 22611-22616.
2. Chames, P.; Baty, D. Bispecific antibodies for cancer therapy: the light at the end of the tunnel? MAbs. 2009, 1(6):539-47.

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