CHAPTER 24 – Evolution of Protein Molecules

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

Enkephalin, a natural ligand for opiate receptors is composed of the pentapepides H-Tyr-Gly-Gly-Phe-Met-OH and H-Tyr-Gly-Gly-Phe-Leu-OH. The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl-Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides.

Identification of two related pentapeptides from the brain with potent opiate agonist activity

The last two decades have been an era of rapid progress in peptide research. This era was begun by the work of Sanger on the amino acid sequence determination of insulin and by du Vigneaud on the structure determination and synthesis of oxytocin. This period has seen impressive progress in the structure elucidation and synthesis of many peptides of natural origin and of great biological significance, as well as in methods for sequence determination and chemical synthesis of peptides [1–4]. Perfection of techniques and instruments for automatic determination of the amino acid sequence of peptides and proteins has made possible a greatly broadened understanding of genetics and evolution as well as the more chemical areas of mechanism of action of enzymes and hormones, and physical chemistry of peptides and proteins. Effective methods of peptide synthesis are crucial to progress in this area, because only by synthesis can adequate amounts of important peptides be made available for chemical, biologi...

Solid Phase Peptide Synthesis

Proteins of moderate size having native peptide backbones are produced by a method of native chemical ligation. Native chemical ligation employs a chemoselective reaction of two unprotected peptide segments to produce a transient thioester-linked intermediate. The transient thioester-linked intermediate then spontaneously undergoes a rearrangement to provide the full length ligation product having a native peptide bond at the ligation site. Full length ligation products are chemically identical to proteins produced by cell free synthesis. Full length ligation products may be refolded and/or oxidized, as allowed, to form native disulfide-containing protein molecules. The technique of native chemical ligation is employable for chemically synthesizing full length proteins.

https://science.sciencemag.org/content/sci/266/5186/776.full.pdf

Synthesis of proteins by native chemical ligation

THE bioassay of adrenocorticotropic hormone (ACTH) based on the increment of adrenal weight in normal 21–23 day old male rats was first suggested by Moon (1937). The general use of such animals has not had widespread acceptance for at least two reasons: (a) the presence of the pituitary in the animal may lead to variable and non-specific results; and (b) the method requires a relatively large dose of the hormone for any significant response. It seemed probable that the sensitivity of the Moon test could be enhanced by injections of a hormone-alum preparation, and the following experiments were carried out to test this point. EXPERIMENTAL The adrenocorticotropic hormone used in these experiments was a highly purified protein preparation isolated from fresh sheep pituitary glands by a modified method of Li, Evans and Simpson (1943). The pitressin-free adrenocorticotropic peptide mixture was obtained by HC1 hydrolysis of the ACTH protein (Li, 1951).

Enhancement of adrenocorticotropic hormone activity by alum in normal 21-day old male rats.

The β-endorphin analog β-endorphin (6-31), although lacking the enkephalin moiety i.e., β-endorphin (1-5) exhibits analgesic activity which is not reversed by naloxone.

β-Endorphin analog

Zone electrophoresis on starch of preparations of follicle-stimulating hormone from sheep pituitary glands.

Some recent knowledge on comparative endocrinology of anterior pituitary adrenocorticotropic, gonadotropic, and growth hormones☆

The effect of various reagents on adrenocorticotropic hormone.

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