Receptor mimicry

Finally, we shall emphasize the successful developments of retro-in-verso (all-D-retro) and end group-modified retro-inverso peptides in several biological areas including hormones [104,105], antibody recognition [106-109], peptide vaccines [110], MHC class II presentation [111,112], protein surface and receptor mimicry [113-115], antibacterial and channel-forming peptides such as mellitin and cecropin A [116,117], intracellular delivery systems [118], and nuclear import [119]. 

Ballesteros, J. A., Shi, L., and Javitch, J. A., Structural mimicry in G-protein-coupled receptors implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors, Mol. Pharmacol., 60(1), 1-19, 2001. 

There is considerable interest in the role of infectious agents in the development of autoimmune diseases. Some of this interest is based on the concept of molecular mimicry as a causal mechanism. Molecular mimicry refers to the possible pathologic role of cross-reactive antibodies or T cells to a self-antigen that is structurally similar to, and thus shares epitopes with, a viral or other infectious agent. For most autoimmune diseases, however, evidence of molecular mimicry leading to disease is not conclusive.1819 Viruses and other infections also have a less-specific immune effect, stimulating toll-like receptors and proinflammatory cytokine secretion, which is another mechanism that has been postulated to influence autoimmune disease risk.20... 

Before the elucidation of the CAR X-ray crystal structure, modeling studies mainly focused on the constitutive activity of the receptor. For example, homology modeling along with molecular dynamics simulations was combined to identify critical amino acid residues responsible for the constitutive activation [43]. Especially, the role of Tyr326 as a molecular mimicry of a bound ligand in the interaction with the AF-2 helix was underscored. Mutational analyses and the later elucidation of the human CAR X-ray crystal structure confirmed an important role of this amino acid for the receptor s constitutive activity [41,44]. 

Taken together, these results suggest that molecular recognition of the dodecapeptide by antibodies differs from its recognition by concanavahn A, and that the immunological cross-reactivity observed in some studies does not reflect structural mimicry. That molecular recognition by concanavalin A of carbohydrates and peptides differs has also been shown in structural studies. Here, the functional molecular mimicry observed with respect to different receptors should not be assumed to imply structural mimicry—the inter-molecular interactions may differ in each case. 

Overall, these chitinase inhibitors provide an interesting example of peptide-carbohydrate mimicry. As described above for several other systems, mimicry consists of a mixture of structurally mimetic interactions and other favorable interactions with the receptor. Of the structurally mimetic interactions, the mimicry by argifin of the N-acetyl group, and part of the pyranosyl... 

These problems have been addressed in a wide variety of imaginative and novel ways and progress in anion complexation has been rapid in recent years " to the extent that it has now been described by Lehn as a full member of the field of supramolecular chemistry. It is important to note that the search for anion-selective receptors has not been limited to the mimicry of Mother Nature s approach. Indeed, a great number of the hosts developed are far from being biocompatible as the tools of the chemist are not limited to the building blocks of natural systems. This aspect of anion recognition chemistry lies at the heart of supramolecular chemistry, the interface between chemistry and biology. ... 

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