Antibody, insulin Monoclonal antibodies

In a protein-binding assay with fluorescence detection a microarray of biotin, HPYPP-peptide and WSHHPQFEK-peptide was screened against streptavidin-Cy3 and avidin-Cy5. By following the same principle an anti-human insulin monoclonal antibody was also screened against a set of different peptides. 

In the selected example by Lam et al. [101] many peptide libraries were prepared using the mix and split technique and tested in different on-bead screens. Incomplete libraries were tested (the population of most of them was more than a million compounds), and the positive structures were exploited through focused libraries. Some libraries were screened against an anti-insulin monoclonal antibody tagged with alkaline phosphatase, which allowed an enzyme-linked colorimetric detection. Only the beads bound to the murine MAb showed a tourquoise color, while the vast majority remained colorless (details of the technical realization of the assay can be found elsewhere [101, 102]). The chemical structure linked to the positive beads was then easily determined via Edman degradation of the peptide sequences. 

Biotechnology era beginning First recombinant DNA products Human insulin Human growth hormone Interferons, etc. Monoclonal antibodies Nucleotide blockage Growth in use of natural products and neutraceuticals... 

After the approval of the first product, recombinant insulin, in 1982, progress in the development of new recombinant protein pharmaceuticals was slow ([10], Fig. 17.1). The number of biotechnology-derived drugs and vaccines approved by the US Food and Dmg Administration (FDA) has increased significantly only since 1995. More recently, sales of biologies have skyrocketed, e.g. from 900 million in 1999 to an estimated 3.5 billion in 2001 for monoclonal antibodies [11]. The annual global market for biopharmaceuticals is estimated to have increased from 12 billion US to 30 billion US in 2003 [12]. 500 candidate biopharmaceuticals are undergoing clinical evaluation and over one hundred protein-based therapeutics are in the... 

Figure 2.8. Scheme of a chimeric peptide with examples for each of the distinct domains. 0X26, anti-rat transferrin receptor monoclonal antibody (mAh) 84-15, anti-human insulin receptor mAh cHSA, cationized human serum albumin VIP, vasoactive intestinal polypeptide DALDA, dermorphin analogue NGF, nerve growth factor BDNF, brain-derived neurotrophic factor PNA, peptide nucleic acid (3-gal, (3-galactosidase. 

With regard to transport capacity, the introduction of the anti-human insulin receptor antibody (HIR MAb) 83-14 as a vector indicates the potential for future improvements in brain-specific delivery vectors. Compared to anti-TfR monoclonal antibodies, the brain de-hvery in primates is over 7-fold higher due to the high PS product of the HIR MAb. 

The dissociation constant (Kd) of a monoclonal antibody with fluorescein isothiocyanate- (FITC)-labeled insulin and unlabeled insulins from several species were measured using CE with laser-induced fluorescence detection (CE-LIF) (9). Kd determinations were made by separating free FITC-labeled insulin and its complex with the antibody in equilibrated solutions in 6 s or less (Fig. 3). Dissociation and association rates for insulin, FITC-insulin, and the antibody are fast enough to reach equilibria in less... 

Wu X, Fan Z, Masui H, et al. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 1995 95 1897-1905. 

Biopharmaceuticals are protein macromolecules, usually prepared by recombinant DNA technology, which are used as therapeutics. This group includes replacement hormones such as insulin, cytokines such as interferons, and monoclonal antibodies. 

Coloma, M.J., et al. 2000. Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor. Pharm Res 17 266. 

Biotech drug development is frequently described as occurring in waves. The initial wave occurred following the introduction of recombinant human insulin in 1982, and comprised recombinant endogenous proteins. The introduction of multiple monoclonal antibodies into pharmacotherapy constitutes the second wave of... 

The scientific and technological achievements of the last decades have allowed the discovery and production of new biological medicines, or substitution of those previously extracted from animal sources, like insulin and growth hormone. Most of those medicines are proteins obtained by animal cell cultivation, which differs from bacteria and yeast in that animal cells carry out post-translational modifications needed for biological activity and similar to the natural protein. Biopharmaceutical production in mammalian cells, including hormones, monoclonal antibodies (mAbs), vaccines, and other molecules with medical interest, involves high cost processes due to factors such as ... 

S12 has been identified in 3-DG-insulin and 3-DG-angiotensin II systems, when heated under physiological conditions at 37 °C and pH 7.6.360 It has also been detected in the kidneys and aorta of diabetic patients using an anti-S12 monoclonal antibody. 

Alternatively, monoclonal antibodies (Mabs) to the relevant receptors can be used as transport vectors. Anti-insulin (Mab83-7 and Mab83-14) and anti-transferrin (0X26) receptor antibodies have been proposed as efficient and selective BBB transport vectors. The antitransferrin receptor antibody binds to a site removed from the transferrin binding site and therefore does not compete with endogenous transferrin for transport across the BBB. Studies using radiolabeled peptides have shown that significant uptake of a... 

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