Nature polypeptides

Certain polymers will exhibit liquid crystal behaviour in solution. This phenomenon was first noted for natural polypeptides, but was found to be obtainable in synthetic systems initially for poly(7-benzyl L-glutamate)... 

The same research group recently carried out the synthesis of other hybrid copolymers in which hydrophobic PS chains had been covalently linked to natural polypeptides such as a lipase enzyme [264], The resulting biohybrid has been referred to as a giant amphiphile and forms catalytic micellar rods in water, as shown in Fig. 17. 

Active sites of enzymes and binding sites of proteins are a general source of instability because they contain groups that are exposed to solvent in order to bind substrates and ligands and so are not paired with their normal types of partners. Stability-activity trade-off is also seen with residues in the natural polypeptide inhibitor of barnase, barstar, that has evolved to bind as rapidly as possible to barnase,70 and also in the active site of T4 lysozyme.71... 

The preparation and characterization of short peptidic molecules that adopt a stable and predictible structure in solution is a prerequisite for the construction of de now-designed artificial enzymes and proteins. In natural polypeptides, the secondary structures are parts of a larger system and their conformational stability is due to several intra- and interchain non-covalent interactions such as van der Waals forces, electrostatic forces, hydrogen bonding, and hydrophobic forces [2], However, these interactions are less important in short... 

This strategy is somewhat reminescent of the biological folding pathways of natural polypeptides that use selective interactions with effectors (Ca2+, chaperone proteins, etc.) to start the nucleation of the secondary structures [5] and has been used successfully to prepare well defined peptide nanostructures by several groups. 

In nature, polypeptides with amphiphilic structures are known to form transmembrane channels formed by an assembly of several helices, so as to present their polar faces inward and their apolar faces outward. In view of such behavior, the photochromic amphiphilic polypeptide was incorporated into a cationic bilayer membrane composed of dipalmitoyl phosphatidyl choline.11201 Fluorescence and microscopic measurements provided evidence that the polypeptide was able to form bundles of helical molecules analogous to their natural counterparts, which acted as transmembrane channels for K+ ions. Irradiation, and the consequent transacts isomerization of the azobenzene link, caused a bending of the molecular structure and a destabilization of the transmembrane bundles. Therefore, formation of ion permeable channels would be favored or inhibited depending on whether the azo moiety... 

Porro, M. Structural basis of endotoxin recognition by natural polypeptides. Trends Microbiol 2 (1994) 65-66. 

Compounds of two amino acids linked by a peptide bond are known as dipeptides those with three amino acids are called tripeptides, and so on. Oligopeptides contain an unspecified but small number of amino acid residues, while polypeptides comprise larger numbers. Natural polypeptides of 50 or more residues are generally referred to as proteins (Chap. 4). 

The other natural polypeptide alkaloids, e.g., the alkaloids of the ergotoxine group (ergoeristine, ergokryptine, and ergocornine) have a spectrum of activity similar to that of ergotamine but their toxic effects are more pronounced. For this reason they have not attained the clinical importance of ergotamine. 

Natural polymer-based networks have also been investigated. The proteins etc comprising antibodies represent the largest group [164, 166, 169, 189] but this is of course a specialised area. Poly(saccharides), in particular starch [60], dextran [161], dextrin [161] and maltohexose [161], and also natural polypeptides, mainly enzymes [162-165], embody the more accessible biopolymers. In some instances imprinting is achieved through formation of covalent bonds, with crosslinkers like cyanuric chloride or glutaraldehyde. Likewise chitin derivatives similarly crosslinked have been exploited [136]. 

Most natural polypeptide chains contain between 50 and 2000 amino acid residues and are commonly referred to as proteins. Peptides made of small numbers of amino acids are called oligopeptides or simply peptides. The mean molecular weight of an amino acid residue is about 110, and so the molecular weights of most proteins are between 5500 and 220,000. We can also refer to the mass of a protein, which is expressed in units of daltons one dalton is equal to one atomic mass unit. A protein with a molecular weight of 50,000 has a mass of 50,000 daltons, or 50 kd (kilodaltons). 

X-ray Diffraction. X-ray diffraction data are a vital part of the foundation supporting the present knowledge of protein structures. Such determinations yield information on three major points (1) the distances and angles between atoms, (2) their planarity, and (3) the tram configuration of the amide group. This section discusses these points, and Sections 10.4.2 and 10.4.3 present some of the uses of x-ray diffraction on synthetic and natural polypeptides. 

Lepirudin, Recombinant Leeches (Hirudo medici-iialis) have been used medicinally for centuries to treat injuries in which blood engorges the tissues. The logic behind this is solid leeches produce an agent known as hirudin that is a potent, specific thrombin inhibitor. Leeches have been used to prevent thrombosis in the microvasculature of reattached digits. Lepirudin (Refludan) is a rDNA-dcrived protein produced in yeast. It has a molecular mass of approximately 7.000 Da. Lepirudin differs from the natural polypeptide, in that it has an N-terminal leucine instead of isoleucine and is missing a. sulfate function at Tyr[Pg.185]

Nature does not stop with glycine as a monomer unit. Instead, any of 20 different a-amino acids are found in most natural polypeptides. In each of these, one of the hydrogen atoms on the central carbon atom of glycine is replaced by another side group. Alanine is the next simplest a-amino acid after glycine it has a... 

The conformations of natural polypeptides have arisen as a consequence of the sequences of amino acids that they contain. In some cases, their biological function does not depend directly on the presence of particular amino acids (e.g., collagen and other connective tissue) whereas, in other cases, certain functional side-chains are mandatory at particular sites in the molecule in order for physiological activity to be shown (enzymes). The correct three-dimensional disposition of these side-chains is obtained through conformational features in their vicinity within the polypeptide and often through features some distance away (Chapter 8). 

The third class of thrombus-imaging peptides are natural polypeptides (disintegrins), with high affinity for the receptor. Disintegrins are usually composed of 48-84 amino acids, and are rich in cysteine residues. The formation of disulfide bridges confer to the polypeptides a defined structure where the RGD motif is exposed at the tip of a flexible loop. Radioactively labeled Bitistatin [127] produced images of intense uptake at the thrombus site which corresponded to the true dimension of the lesion. 

Proteins Large natural polypeptides, such as globular proteins u.sed as enzymes, ftbrotis proteins in muscle, and hemoglobin. 

Surgeons have used medicinal leeches Hirudo medicinalis) for years to prevent thrombosis in fine vessels of reattached digits. Hirudin is the potent, specific thrombin inhibitor isolated from the leech. Lepirudin is a rDNA-derived (recombinant yeast) polypeptide that differs from the natural polypeptide, having a terminal leucine instead of isoleucine and missing the sulfate group at Tyr 63 (115). 

Heme group The oxygen-carrying porphyrin substituent in the natural polypeptides myoglobin and hemoglobin. 

The permeases of other neurotransmitters have been isolated, but not in quantity. All appear to be glycoproteins, highly phosphorylated. The isolation of catecholamine receptors is described in Section 12.4. The receptors for the natural polypeptide analgesics, which also bind morphine, are discussed in Section 12.8. 

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