Pharmacokinetics and biodistribution effects of certain fusi | 95381
International Research Journals

International Research Journal of Biochemistry and Bioinformatics

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Pharmacokinetics and biodistribution effects of certain fusion proteins on recombinant protein polymer and antibody


Emily Antonio*

There is growing evidence that protein domains or inherently unstructured proteins serve crucial biological purposes. The polymer theory, which was created to forecast the general physical characteristics of polymers, can be usefully used to the analysis of these kinds of proteins. These theories "coarse-grain" the molecular information out of the models and replace it with a few of constants that define the polymer. This decrease in complexity makes it possible to study very large systems. The time scales that are available also greatly expand in the case of simulations. Here, we talk about how unstructured proteins can be categorised within a polymer framework and how polymer theory can be applied to them. In order to predict functionally significant properties like gyration radius, height of a polymer brush, and force needed to compress a polymer brush, we then review polymer theory (Pavia et al., 2020).

Alternative non-IgG binding proteins created for therapeutic purposes are compact and, as a result, are quickly removed from the bloodstream by renal filtration. Extensions of unfolded polypeptides have been developed to prolong serum half-life in order to avoid repeated injection or continuous infusion for the maintenance of therapeutic serum concentrations, but systematic, comparative studies examining the impact of their size and charge on serum half-life, extravasation, tumour localization, and excretion mechanisms have yet to be conducted (Gurusamy et al., 2013). In a preclinical tumour xenograft model in mice, we employed a high-affinity Designed Ankyrin Repeat Protein (DARPin) targeting the tumour marker epithelial cell adhesion molecule (EpCAM) and fused it with a number of predetermined unstructured polypeptides. We did a detailed comparative localization, distribution, and extravasation investigation using three different sizes of two previously known polypeptides—an uncharged one called PAS that only contains Pro, Ala, and Ser and a charged one called XTEN that contains Pro, Ala, Ser, Thr, Gly, and Glu. With a half-life of up to 21 hours in mice, pharmacokinetic study demonstrated a clear linear association between hydrodynamic radius and serum half-life for both polypeptides. EpCAM was required for tumour uptake, which was directly correlated with half-life and tumour growth and demonstrated uniform tumour penetration for all fusion proteins without unintended accumulation in non-target tissue. Unexpectedly, charge had no effect on any measure, including renal elimination kinetics, tissue accumulation, tumour, or tissue accumulation. Thus, the potential for precise half-life alteration and tumour targeting is essentially similar for both types of polypeptides (Banani et al., 2017).

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