Chimerical amino acids

Che, Y., and Marshall, G. R. (2006) Engineering cyclic tetrapeptides containing chimeric amino acids as preferred reverse-turn scaffolds. J. Med. Chem. 49, 111-124. 

Wessig, R, Stereoselective synthesis of novel chimerical amino acids via a photochemical key step, Synlett, 1465, 1999. 

Mice immunized intranasally with chimeric PVX particles expressing a six-amino-acid neutralizing epitope from gp 41 of HIV-1 produced high levels of HIV-l-specific IgG and IgA antibodies [50], The anti-H66 IgG titers ranged from 2000 to >30,000. Mice immunized intranasally produced IgA in the serum and in fecal extracts. 

Fig. 5. The triple //-spiral in the adenovirus fiber shaft. (A) The triple //-spiral domain alone. Shown are amino acids 319-392 of each of the three chains, forming four triple /1-spiral repeats (van Raaij et al, 1999b). (B) Structure of a chimeric adenovirus fiber shaft-fibritin foldon domain protein (Papanikolopoulou et al, 2004b).

The production of chimeric cDNA molecules is typically used to localize an amino acid domain in a protein that gives rise to a specific property that is absent in a homologous protein. For example, this property could be the recognition of a specific drug, interaction with a specific protein, or localization to a specific cellular location. Chimeras are often a necessary first step in the path of identifying individual... 

Chimeric enzymes constructed fi"om two different angiosperms (Panax ginseng, Araliaceae, and Arabidopsis thaliana, Brassicaceae) yielded mixtures of triterpenoids, p-amirin and lupeol, at a composition depending on the particular chimera methyl scrambling was observed for lupeol only (Kushiro 1999). A few differences in the amino acids at the active site are responsible for these effects. This implies that the high variety of plant triterpenoids owes more to chimeric enzymes than product-specific triterpene synthases. It was proposed that these chimeric enzymes act as multifunctional triterpene synthases (Kushiro 1999). 

Substrate specificity between DHK, DHQ, and DHM appears, based on chimeric DFR proteins formed using the P. hybrida and Gerbera hybrida sequences, to locate to a 26 amino acid region that may be the binding pocket for the B-ring, and as little as one amino acid change in this region can alter the specificity of the enzyme. ... 

To further reduce the immunogenicity of a chimeric antibody, researchers designed humanized antibodies that replace all mouse amino acid sequences except the hypervariable CDR domains of Ig that represent only a small fraction of the Fv fragment. Some humanized antibodies are now approved for clinical use and many more are being tested for an array of therapeutic indications (Tables 10.4 and 10.5). 

A basic understanding of the structure of the BCR-ABLl chimeric protein is important to understanding how the multiple mutations that have been described in the ABLl kinase domain cause resistance. The c-ABLl protein is expressed in two splice forms that are known as la and lb (Fig. 1C). The la form is 19 residues shorter than lb. The lb form contains a myristoylation site on its second residue. The second residue is a glycine that appears to help regulate enzymatic activity, and its mutations to alanine prevents myristoylation and results in an activated kinase (50). The lb form also contains a cap region that is believed to stabilize the inactive eonfirmation of the kinase (51). The numbering system used to identify the amino acid residues where mutations occur is based on the shorter la form. 

In addition to the C-terminus, several other regions of Ga have been implicated in receptor binding by a variety of experimental approaches (Fig. 4). Residues in the a4//16 loop contribute to the binding surface as demonstrated by alanine-scanning mutagenesis (Onrust et al, 1997), studies with chimeric Ga proteins (Bae et al., 1997, 1999), sequence analysis of conserved amino acids in Ga subclasses (Lichtarge et al., 1996), chemical cross-linking (Cai et al, 2001), and protection from tryptic proteolysis (Mazzoni and Hamm, 1996). The C-terminal 11 amino acids of Gat and... 

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