Proteins general

Standardization and Testing". RequHemeats are geaerally specified within Hceases Hi the United States, and include a variety of Hi-process tests to assess purity, safety, and potency of the iadividual components and potency and safety of the final product. Potency is standardized by determining the size of the conjugate and the quantitative amount of saccharide that is bound to the carrier protein. General safety and immunogenicity is assessed Hi animals. 

Water-soluble polymers and polyelectrolytes (e.g., polyethylene glycol, polyethylene imine polyacrylic acid) have been used success-hilly in protein precipitations, and there has been some success in affinity precipitations wherein appropriate ligands attached to polymers can couple with the target proteins to enhance their aggregation. Protein precipitation can also be achieved using pH adjustment, since proteins generally exhibit their lowest solubility at their isoelectric point. Temperature variations at constant salt concentration allow for frac tional precipitation of proteins. 

This section briefly reviews prediction of the native structure of a protein from its sequence of amino acid residues alone. These methods can be contrasted to the threading methods for fold assignment [Section II.A] [39-47,147], which detect remote relationships between sequences and folds of known structure, and to comparative modeling methods discussed in this review, which build a complete all-atom 3D model based on a related known structure. The methods for ab initio prediction include those that focus on the broad physical principles of the folding process [148-152] and the methods that focus on predicting the actual native structures of specific proteins [44,153,154,240]. The former frequently rely on extremely simplified generic models of proteins, generally do not aim to predict native structures of specific proteins, and are not reviewed here. 

Immunophillins are abundant proteins that catalyze the cis-trans isomerization of proline residues within proteins, generally to aid in protein folding. Immunophillins are not essential proteins, are the intracellular binding proteins of several immunosuppressive drugs. Cyclosporin A exerts its action after binding to cyclophilin. Tacrolimus and sirolimus predominantly bind to the protein FKBP-12 (FK binding protein-12). 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Loss of the native conformation of a protein generally exposes hydrophobic amino acid residues that are normally buried on the inside of the self-associated structure and are shielded from the aqueous environment. This leads to association between the exposed hydrophobic residues of neighboring proteins (aggregation) or between these exposed residues and hydrophobic surfaces that the protein may encounter either in the manufacturing process or in the primary package. 

The denaturation of proteins generally involves at least partial unfolding, with the loss of secondary and tertiary structure. In the present context, we are interested in the end point of this process — proteins that are unfolded to the maximal extent by various agents heat, cold, acid, urea, Gdm-HCl.1 Three major questions concerning unfolded proteins are of interest in the present chapter. Do different unfolding agents... 

Some proteins, generally with limited molecular weight, are expressed at high levels as a response to thermal shocks. 

Higher molecular mass dextrans (partieularly dextran 70, 75 and 110) are used to promote short-term expansion of plasma volume thus preventing/treating shoek due to blood loss. A 6% w/v solution of these dextrans exerts an osmotie pressure similar to that of plasma proteins. Generally, an initial dose of 500 ml 1 litre is administered by i.v. infusion. Dextrans also inhibit the aggregation of red blood eells. Thus, they are often used to prevent/treat post-operative thrombo-embolic disorders (see later in this ehapter) and to improve blood flow. 

It denatures proteins, general protoplasmic poison (but acts slowly). Broad spectrum germicide. 

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