Synthetic amino acids

Dansylated amino acids Synthetic 0.1 jtmol L"1 (glutamine)... 

Primary amino acids Synthetic 0.06 pmol (alanine)-1 pmol (ser-... 

Deacylation ofp-nitrophenyl esters of amino acids Synthetic vesicles + dipeptide nucleophiles. High stereoselectivity observed Ohkubo et al., 1982... 

A. General description Bivalirudin, a 20 amino-acid synthetic peptide, is a direct thrombin inhibitor. It is an analogue of recombinant hirudin (Refludan), a 65 amino-acid anticoagulant derived from the leech. The molecular weight of bivalirudin is about 2.2kDa (anhydrous free base peptide). 

Enfuvirtide (Fuzeon , T-20, Ro 29-9800, Hoffmann-La Roche) is a 36-amino acid synthetic peptide with a molecular weight of 4492 Da. It selectively inhibits human immunodeficiency virus (HIV) fusion to the host cell membranes [73]. The N-terminus of the molecule is acetylated and the C-terminus is amidated. A metabolite, M-20, is deamidated at the C-terminus. An ELISA method was initially used during drug development of this compound, but the decision was made to develop and validate an LC-ESI-MS/MS method for the simultaneous determination of enfuvirtide and M-20 for PK studies to support the NDA submission of this product [53]. Some of the issues of LC-ESI-MS/MS application for peptide bioanalysis are highlighted in the following. 

Cassataro, J., Estein, S.M., Pasquevich, K.A., et al. (2005) Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infect. Immun. 73(12), 8079-8088. 

Jia et al. (2001) have identified a 12-amino-acid synthetic peptide derived from exon 6 (based on sequence of VEGF189) that inhibits VEGF binding to HUVECs and porcine aortic ECs. It also inhibits VEGF-stimulated ERK activation and prostacyclin production. The peptide blocks the interaction of VEGF with KDR and neuropilin-1. 

S,l S,2 S,3 if)-2-(2 -Carboxy-3 -phenylcyclopropyl)-glycine (= PCCG-IV)] (cyclic aliphatic amino acid) Synthetic mGlu-K (Class 11) antagonist Class II 2 (8)... 

Saitoh, A., Achiwa, K., Tanaka, K., Morimoto, T. Versatile Chiral Bidentate Ligands Derived from a-Amino Acids Synthetic Applications and Mechanistic Considerations in the Palladium-Mediated Asymmetric Allylic Substitutions. J. Org. Chem. 2000, 65, 4227 240. 

Deacylation of p-nitrophenyl esters of amino acids Synthetic vesicles 4- histidine-functionalized surfactant. Cholesterol increased rates and enantioselectivity Ueoka and Matsumoto, 1984... 

The synthesis of certain enzymes may also be specifically inhibited. In a process called repression, the end product of a biochemical pathway may inhibit the synthesis of a key enzyme in the pathway. For example, in E. coli the products of some amino acid synthetic pathways regulate the synthesis of key enzymes. The mechanism of this form of metabolic control is discussed in Chapter 18. 

The amino acids differ from other classes of biomolecules in that each member of this class is synthesized by a unique pathway. Despite the tremendous diversity of amino acid synthetic pathways, they have one common feature. The carbon skeleton of each amino acid is derived from commonly available metabolic intermediates. Thus in animals, all NAA molecules are derivatives of either glyc-erate-3-phosphate, pyruvate, a-ketoglutarate, or oxaloacetate. Tyrosine, synthesized from the essential amino acid phenylalanine, is an exception to this rule. 

A. Saitoh, K. Achiwa, K. Tanaka, and T. Morimoto, Versatile chiral bidentate ligands derived from a-amino acids. Synthetic applications and mechanistic considerations in palladium-mediated asymmetric allylic substitutions, J. Org. Chem., 65 (2000) 4227-4243. 

Enfuvirtide is a 36-amino-acid synthetic peptide whose sequence is derived from a part of the transmembrane pg41 region of HIV-1. Enfuvirtide is not active against HIV-2 but has a broad range of potencies against HIV-1 isolates. 

To overcome this problem, PAMAM dendrimers have been modified and/ or used at lower generations. Skoza and colleagues covalently attached GALA, a 30 amino acid synthetic peptide, with a glutamic acid-alanine-leucine-alanine repeat, to PAMAM dendrimers and observed that the transfection efficiency was enhanced. In another approach, PAMAM dendrimers were covalently linked with cyclodextrin macrocycles to create a synergic effect between dendrimer and cyclodextrin. To enhance PAMAM transport into cells, a series of artificial proteins were designed by... 

Enfuvirtide is a 36 amino acid synthetic peptide used for managing HTV treatment-experienced patients. It is in powder form and must be reconstituted with sterile water for subcutaneous administration. The adult dose is 90 mg bd. Absorption does not vary by site of injection (for example, thigh, arm, or abdomen) [211 ]. Enfuvirtide binds to HR 1, blocking a conformational change on gp41 required for the fusion of the lipid envelope of HIV to the cytoplasmic membrane of CD4 T lyi ho-cytes, thus preventing viral entry [212 q. 

Solution Phase Synthesis of the Pulmonary Surfactant KL4 A 21 Amino Acid Synthetic Protein... 

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