Proceedings book download - 5Z.com

Fig. 3. Activity of CovX-Bodies in 125 IMgTX Competiton Binding Assay.CovX Technology: Tethering and conjugating the toxin peptide to the AntibodyPeptides and monoclonal antibodies have emerged as important therapeutics, but each haslimitations. Peptides are highly potent, but undergo rapid degradation in the body andrequire frequent administration. Traditional monoclonal antibodies have more favorablepharmacokinetics, but constrained by a challenging and lengthy development process. TheCovX technology is based on a novel approach that addresses these limitations bycombining the strengths of peptides and antibodies into a new molecule. This molecule,called a CovX-Body, is created by covalently joining, after appropriate tethering viaproprietary linkers, a pharmacophore to the binding site of a specially designed antibody(CVX-2000); effectively reprogramming the antibody (see Figure 2). The conjugation ofthe toxin to the antibody was achieved by using a 2:1 molar ratio of the peptide with CVX-2000 Antibody (20 mg/ml, pH 6.5).Binding affinity of CovX-Bodies for Kv1.3 was assessed by a I125-MgTx competitionbinding assay (Figure 3). Dilutions of test compound were incubated in presence of aconstant amount I125 MgTx over membrane preparations made from a Kv1.3overexpressing L929 cell line. After incubation, membrane preps were washed to removeunbound I125 MgTx and CovX-Body affinity of the Kv1.3 channel was determined bymeasuring residual I125-MgTx.ConclusionsWe described an efficient and simple way to achieve the synthesis and folding of complexpeptides such as the toxin peptide containing a specific pattern of three disulfide bridges. Atthe same time we showed the conjugation of those peptides to the antibody CVX-2000 andreported preliminary activity data in binding the Kv1.3 ion channel. Further investigationsare on the way to assess the stability and the pharmacokinetic of those compounds.109