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VH H VH H Camelid sdAb development C H2 Fc C H3 A novel approach to anƟbody discovery from GenScript Single Domain Antibody (sdAb): Camelids naturally produce antibodies composed only of heavy chains as compared to the conventional antibodies (see below). The antigen-binding site of these unusual heavy chain antibodies is formed only by a single heavy chain variable domain, designated as single domain antibodies (sdAbs). sdAbs combine the advantages of conventional antibodies with important features of smaller molecule sdAb drugs. The unique and well-characterized properties of sdAbs make them ideal building blocks for various antibody-based applications. GenScript offers a comprehensive set of services for sdAb research and development. Advantages of sdAbs as compared to conventional antibodies: Ability to bind “hidden” epitopes especially in challenging targets Ability to bind into cavities or active sites of protein targets Pure monomer Better tissue penetration, even penetrating blood-brain-barrier Excellent stability Easier to engineer bi-specific and tri-specific antibody Advantages of Choosing GenScript: VH C H1 VL VH H VH H CL C H2 C H2 C H3 C H3 ConvenƟonal IgG Camelid heavy chain anƟbody Two heavy chains Two heavy chains Two light chains No light chain Twelve protein domains Six protein domains Full Fc Full Fc sdAb A leading sdAb service provider with seasoned scientists and proprietary technologies Owns exclusive patents on technologies related to sdAb optimization Ability to engineer sdAbs capable of achieving extremely high affinity (KD= 4 pM) A recognized service provider for sdAb-based therapeutics for major pharmaceutical companies Routes for sdAb generation: Direct sdAb isolation from naive sdAb phage display library (1010 diversity) containing camel, llama and alpaca sdAb repertoire. Generation of high affinity sdAbs by camelid immunization and subsequent antibody engineering work. Approaches for llama immunization: DNA immunization Cell immunization Lipoparticles immunization Protein immunization Peptides immunization Combination immunization Technical platforms: Phage display platform Yeast surface display platform FASEBA screening platform Epitope binning platform Kinetic determination platform Featured Services: 120 Development of a panel of new antibody drugs, targeting a key cytokine in cell growth 100 Candidate 2 80 Candidate 3 % Cell Viability Case 1: An immunized sdAb phage display library was constructed from PBMCs after animal immunization. A panel of sdAbs with good expression, high stability and affinity were isolated using GenScript’s patented technology-FASEBA platform. Three independent sdAbs were identified based on high-affinity binding to the antigen, and were evaluated by a cytokine-induced cell-proliferation assay. As shown by the data in the graph below, their potency of inhibitory activity was determined to be indistinguishable from that of a marketed traditional antibody drug against the same cytokine. Candidate 1 Marketed Antibody Drug 60 40 20 0 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 Ab Concentration, [μg/ml] Inhibition of cells proliferation by marketed antibody drug and top three sdAb candidates 25 Development of a high affinity sdAb, as a valuable reagent An sdAb phage display library was generated using PBMC and spleen lymphocytes. sdAb swere isolated and characterized from this library, and the lead sdAb exhibits good specificity and extremely high affinity. The specificity and high affinity were validated by Biacore. The small dimension (15 KDa,4×2.5×3 nm) of sdAb and super high affinity make it excellent probe in biosensor applications. 100 nM 20 Response RU Case 2: 25 nM 15 6.25 nM 10 6.25 nM repeat 5 1.56 nM 0.39 nM 0 0 500 1000 1500 2000 Time s Sensorgram of affinity measurement of the lead sdAb Kinetics of the high affinity sdAb Case 3: Isolate sdAb for supporting protein crystallization kd (1/s) KD (M) 5.73E+05 3.92E-05 6.83E-11 1.6 Absorbance/450nm sdAbs are versatile crystallization chaperone that has been recognized in this field. sdAb has a highly structured β-sheet core that provides a rigid scaffold for stabilizing potential intra-crystal contacts. In this case, a batch of sdAbs was isolated from GenScript’s ready-to-use naïve libraries, which specifically recognize activated GPCR complexes but not ligand or inactivated GPCR. After two rounds of subtractive panning, the phage binders were enriched up to 6,000 fold. The sdAbs were chosen for supporting GPCR crystallization. ka (1/Ms) Activated GPCR Inactivated GPCR | Toll-Free: 1-877-436-7274 | 0.8 0.4 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Several binders were obtained to positively recognize activated GPCR only Tel: 1-732-885-9188 | Fax: 1-732-210-0262 | Email: [email protected] All Rights Reserved. All content described by GenScript is copyright of GenScript Corporation unless specifically identified otherwise. This includes all imagery, text and programmatic computer code. Blocking buffer 1.2 www.genscript.com 860 Centennial Ave., Piscataway, NJ 08854, USA Ligand - +