Functional mimetics

While the a-helix of L-a-peptides and the (M)-3i4 helix of the corresponding peptides have opposite polarity and helicity (see Section 2.2.3.1), the inserhon of two CH2 groups in the backbone of L-a-amino acids leave these two hehx parameters unchanged, both the a-helix and the 2.614-hehx of the resulting y" -peptides being right-handed and polarized from N to C terminus. In view of these similarities, the y-peptide hehcal fold might prove useful as a template to elaborate functional mimetics of bioachve a-polypeptides. 

Although biologically active helical y-peptides have not been reported so far, the striking structural similarities (polarity and helicity) between the a-helix of L-a-peptides and the (P)-2.6i4-hehx of y-peptides suggest that the 2.614-helical backbone might prove useful as a template for elaborating functional mimetics of a-helical surfaces and intervening in protein-protein interactions. 

Song, J. and Ni, F. (1998) NMR for the design of functional mimetics of protein-protein interactions one key is in the building of bridges, Biochemistry and Cell Biology 76,177-18. 

Type II Functional mimetics Molecular modeling, HTS GPCR antagonists... 

Glycomimetics Linked sugars Spaced sugars Functional mimetics Saccharide-peptide hybrids Sugar amino acids Solid phase synthesis Sialyl Lewis Carbohydrate medicinal chemistry... 

G. Tuchscherer, Template assembled synthetic proteins (tasp) as functional mimetics of proteins, Angew. Chem., lnt. Ed. Engl. 1996, 35, 1482. 

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

The fluidity is one of the most vital properties of biological membranes. It relates to many functions involved in biological system, and effective biomembrane mimetic chemistry depends on the combination of both stability and mobility of the model membranes. However, in the polymerized vesicles the polymer chain interferes with the motion of the side groups and usually causes a decrease or even the loss of the fluid phases inside the polymerized vesicle (72,13). 

M. Dubber and T. K. Lindhorst, Synthesis of carbohydrate-centered oligosaccharide mimetics equipped with a functionalized tether, J. Org. Chem., 65 (2000) 5275-5281. 

Some non-silica sol-gel materials have also been developed to immobilize bioactive molecules for the construction of biosensors and to synthesize new catalysts for the functional devices. Liu et al. [33] proved that alumina sol-gel was a suitable matrix to improve the immobilization of tyrosinase for detection of trace phenols. Titania is another kind of non-silica material easily obtained from the sol-gel process [34, 35], Luckarift et al. [36] introduced a new method for enzyme immobilization in a bio-mimetic silica support. In this biosilicification process precipitation was catalyzed by the R5 peptide, the repeat unit of the silaffin, which was identified from the diatom Cylindrotheca fusiformis. During the enzyme immobilization in biosilicification the reaction mixture consisted of silicic acid (hydrolyzed tetramethyl orthosilicate) and R5 peptide and enzyme. In the process of precipitation the reaction enzyme was entrapped and nm-sized biosilica-immobilized spheres were formed. Carturan et al. [11] developed a biosil method for the encapsulation of plant and animal cells. 

Endocrine disruptors apparently affect all nuclear receptors. Thus, a notable increment in impotence, alterations of the libido and of oligospermia in workers exposed to pesticides has been described. These alterations are due to the action of some compounds with estrogen-mimetic action and to their interaction with the androgen receptor. Additionally, alterations of thyroid function have been detected in rats exposed to dioxin and other toxic agents,... 

A similar approach was used in the synthesis of the sialyl Lewis X mimetics of type 85 (Scheme 13.22).66 Protein crystallization,67 conformational studies of sLex in solution68 and in bound form to E- and P-selectin69 as well as the study of structure-function relationships70,71 gave information about the functional groups of the sLex-epitope essential for the binding to the selectins. Synthesized mimetics must contain the three essential hydroxyl functions of the fucose. Sialic acid, galactose, and... 

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