Amino acids modifications

Sulfoxide Mutant Amino acid modifications" sulfoxide ee sulfone... 

Klapper I, Hagstrom R, Fine R, Sharp K, Honig B (1986) Focusing of Electric Fields in the Active Site of Cu-Zn Superoxide Dismutase Effects of Ionic Strength and Amino-Acid Modification. Proteins 1 47-59. 

Grabarse WG, Mahlert F, Shima S, et al. 2000. Comparison of three methyl-coenzyme M reductases from phylogenetically distant organisms unusual amino acid modification, conservation and adaptation. J Mol Biol 303 329 4. 

By using recombinant DNA techniques, modifications in the protein backbone, such as additions, deletions and alterations of amino acids, are easily achieved. These modifications can contribute to improved pharmacokinetic properties of the construct. Additions may consist of the introduction of residues that allow covalent conjugation of drug molecules. Deletions of amino acids can employed to remove membrane-bound regions of a protein, thereby increasing its solubility. Single amino acid modifications can be used to minimize antibody responses and alter the binding specificity and/or the three-dimensional structure of a certain protein. 

Rapid-acting insulin analogues (lispro, insulin aspart [Humalog, Novo log]) have been engineered to contain amino acid modifications that promote rapid entry into the circulation from subcutaneous tissue. They begin to exert their effects as early as 5 to 10 minutes after administration. Lispro insulin, the first insulin analogue to be approved in Europe and the United States, is produced by switching the positions of lysine-proline amino acid residues 28 and 29 of the carboxy terminus of the p-chain. Lispro insulin displays very similar actions to insulin and has a similar affinity for the insulin receptor, but it cannot form stable hexamers or dimers in subcutaneous tissue, which promotes its rapid uptake and absorption. 

AMINO ACID MODIFICATION OF SUNFLOWER PROTEIN ISOLATE DUE TO ALKALINE TREATMENT1..2... 

Parry and Steinert (1999) noted that posttranslational modifications were found almost (but not quite) exclusively in the head and tail domains of all IF proteins. Nothing in the five years since their review has changed that conclusion, though more examples of amino acid modification are now known. A selection of posttranslational modifications is noted below, but a comprehensive list has not been attempted and is considered beyond the scope of this review. Useful references to posttranslational modifications include those of Quinlan et al. (1994), Parry and Steinert (1999), and Herrmann and Aebi (2000). 

Searching for amino acid modification http //pir.georgetown.edu/pirwww/dbinfo/resid.html Searching for protein motifs http //scansite.mit.edu... 

MALDI-TOF provides limited capabilities for mixture analysis, LC/MS methods are used to provide more detailed interrogation of protein expression and peptide sequence. The use of LC/MS approaches for protein identification in conjunction with 2-DGE offers distinct advantages such as the ability to handle low picomole (miniaturized) level samples, enhanced separation, detection, the amenability to N-terminally blocked proteins, and fast analysis. The LC/MS methods for protein characterization focus on four distinct goals (1) confirmation of putative sequence, (2) identification of amino acid modifications, (3) identification of known proteins, and (4) sequence determination of unknown proteins. 

More yS-amino acids are, apparently, special building blocks within natural (cyclo)peptides and depsipeptides [11]. It is not dear whether Nature aimed at an increase of proteolytic stability or at conformational modification. Chemists, however, followed this example of natural / -amino acid chemistry decades ago and started to modify known a-peptides by substitution of solitary a-amino adds with p-amino acids [12]. One major issue of this synthetic analoging was to increase the proteolytic stability of peptides [13, 14] with regard to peptidases [15]. A second goal was the controlled conformational tuning of cyclo-a-peptides with / -amino acid modifications. 

Other methods of stabilization include chemical or carbohydrate modification of enzymes. Modifications of reactive groups on proteins without insolubilization has been used to enhance stability in solution. Grafting of polysaccharides or synthetic polymers, alkalation, acetylation and amino acid modification have all been reported (5)... 

Focusing of Electric Fields in the Active Site of Cu-Zn Superoxide Dismutase Effects of Ionic Strength and Amino-Acid Modification. 

Also in the prediction of the introduction of new epitopes by protein modification immune-tolerant transgenic mice can be used. Mice transgenic for human insulin and tissue plasminogen activator have been used to identify new epitopes in products with amino acid modifications [14,15],... 

Klapper, I.K., Hagstrom, R., Fine, R., Sharp, K., and Honig, (1986) Focusing of electric fields in the active site of Cu-Zn superoxide dismutase effects of ionic strength and amino acid modification, Proteins, 1,47-59. 

Feng L, Sheppard K, Namgoong S, Amhrogelly A, Polycarpo C, Randan L, Tumhula-Hansen D, Soil D. Aminoacyl-tRNA synthesis by pre-translational amino acid modification. RNA Biol. 2004 1 16-20. 

List of mass shifts due to amino acid modification. 

One final interesting amino acid modification is that found in the methanogenic Archaea. These bacteria interpret the amber stop codon as the amino acid methylpyrrolysine, making this the 22" genetically encoded amino acid (the 21 being the N-formyl methionine that eukaryotes use to start translating all their proteins). 

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