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De Novo Single Domain Antibody Sequencing Service

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Creative Biolabs is pleased to introduce an unparalleled de novo single domain antibody sequencing service, which has been developed, based on our world-leading platform of de novo antibody sequencing using our proprietary Database Assisted Shotgun Sequencing (DASS) technology. Soluble and functional single domain antibody can be sequenced by subunit with 100% coverage of VHH regions as well as excellent accuracy, and dozens of successful cases proved with 100% accuracy.

Single domain antibodies are derived from a particular type of antibodies that exist in the blood of camelids (llama, alpaca, camel, dromedary, etc). In contrast to conventional antibodies that exist in all mammals (including human beings), the camelid “heavy-chain antibodies” (HCAbs) lack a light chain (the green domains in Fig.1). While conventional antibodies bind to antigen through the assembly of the variable domain of the heavy chain (VH) and that of the light chain (VL), the camelid HCAbs bind to antigen with a single domain called the VHH because of its size in the nm range, can be easily produced in bacteria or yeast in large quantities, is very stable and binds to the antigen with high affinities and specificities.

Fig. 1 Comparison between conventional Ab and camelid HCAb.

Single domain antibodies combine the advantages of conventional antibodies with important features of small molecule drugs. Like conventional antibodies, single domain antibodies show high target specificity, high affinity for their target and low inherent toxicity. However, like small molecule drugs they have the opportunity to inhibit enzymes and readily access receptor clefts, which is challenging with conventional antibodies.

Fig. 2 Basic strategy of mass spectrometric de novo sequencing

The full length of the single heavy chain camelid antibody (VHH) sequence could be obtained by mass spectrometric de novo sequencing. Leu/Ile ambiguities could be resolved by homology comparisons with known VHH sequences (Fig. 2).

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