Peptides physiological activity

Folding of a peptide probably occurs coincident with its biosynthesis (see Chapter 38). The physiologically active conformation reflects the amino acid sequence, steric hindrance, and noncovalent interactions (eg, hydrogen bonding, hydrophobic interactions) between residues. Common conformations include a-helices and P pleated sheets (see Chapter 5). 

Neurotransmitters produce physiological responses in nano- or micromolar (10 to 10 concentrations, whereas peptides are active in picomolar (10 concentrations. 

In comparison to the level of cellular serine or threonine phosphorylation, protein tyrosine phosphorylation occurs at quite low levels in normal cells but dramatically increases upon oncogenic transformation or stimulation. Since the first discovery in 1978 that the transforming protein from Rous sarcoma virus (pp60vsrc) exhibited intrinsic kinase activity/5 protein kinase activity has also been shown to be inherent to other growth factor receptors such as epidermal growth factor receptor and the insulin receptor,[6 91 and to involve autophosphorylation processes. The diverse biochemical activity exhibited by protein tyrosine phosphorylation has stimulated the development of chemical methods for the preparation of phosphorylated peptides for use as substrates in elucidating the biochemical and physiological activity of phosphorylated site(s). 

Nanotubes are functionalised to improve their solubility in water or to attach to their surface biologically active substances such as peptides and drugs. The ability to attach biological substances has raised an interest in using nanotubes as carriers for delivery of drugs and vaccines. A number of researchers performed functionalization of CNT with physiologically active molecules and macro-objects. These results are summarized in Table 2.3 [30 0]. 

Kawamura, Y., Takane, T., Stake, M., and Sugimoto, T. (1992). Physiologically active peptide motif in proteins Peptide inhibitors of ACE from the hydrolysates of Antarctic krill muscle protein. Jpn. Agric. Res. Quart. 26, 210-213. 

Figure 25-9 Some important physiologically active peptides...

Another factor that can influence the distribution of therapeutic peptides and proteins is binding to endogenous protein structures. Physiologically active endogenous peptides and proteins frequently interact with specific binding proteins involved in their transport and regulation. 

Several of the small physiologically active peptides now are known to be derived from a single protein precursor synthesized by the pituitary gland (43). As shown in Figure 9, ACTH (adrenocorticotropic hormone), /3-LPH ( -lipotropic hormone), /3-MSH ( -melanocyte-stimulating hormone), /3-endorphin, and enkephalin result from the specific proteolytic cleavage of a precursor protein of approximately 8,000 daltons. 

In ABL, an early step in apoB lipoprotein assembly shared by intestinal and liver cells is defective. The net result is near absence of all plasma apoB lipoproteins. ApoB synthesis from a mRNA transcript occurs, but its successful assembly into the mature lipoprotein particle does not. The inability to assemble apoB into lipoproteins was shown to be due to a defect in the mttp gene in affected individuals (Wetterau et al., 1992). Its translational product is an 894-amino acid, 97-kd, polypeptide that exists in the ER complexed with a 55-kd protein disulfide isomerase which is believed to maintain solubility, physiologic activity, and ER retention of the 97-kd peptide. The heterodimeric complex of the 97-kd and 55-kd subunits is referred to as microsomal triglyceride transfer protein (MTP) (Wetterau et al., 1992). 

Gastrin is a hormone released from the stomach that controls the progress of digestion. Early work on the hormone showed that only the four C-terminal amino acids of the peptide were necessary for its physiological activity. 

An efficient, highly regioselective, synthesis of fluoro amino acids could have particular significance in medicinal chemistry and pharmacology, because of the increasing interest in the incorporation of fluoro amino acids into physiologically active peptides. 

CCK is a linear polypeptide that exists in multiple molecular forms. The first form isolated was the 33-amino acid peptide CCK-33. Other major forms are CCK-8, CCK-39, and CCK-58. In all forms, the five C-terminal amino acids are identical to those of gastrin and are necessary, together with a sulfated tyrosyl residue, for physiological activity. All of the forms of CCK are produced by enzymatic cleavage of a single 115-amino acid precursor, preprocholecystokinin. 

Clarification of rough beer, vinegar and pasteurization of clarified beer by cross-flow ultrafiltration are also very common processes utilizing hollow fiber ultrafiltration. As seen in Table 1, an important number of membrane manufacturers specialize in medical and pharmaceutical applications. In pharmaceutical and biotechnology industries, hollow fiber membranes are used for the concentration, separation, and purification of physiological activators such as antibiotics, vaccines, enzymes, proteins and peptides, as well as blood purification (hemofiltration). As a physical barrier for bacteria and viruses, membranes are also a popular option for the production of purified water for hospitals and pharmacies. 

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