Amino acid, terminally blocked

In 1991, Newkome and Lin 121 reported a series of acid terminated poly(ether amido) dendrimers (e.g., 3, 4), generated from the tetraacid core (1) and sequential use of the amino acid building block 2 (Scheme 7.1). These acid-terminated dendrimers were readily transformed 131 into the related polytryptophane analogues (5-7) by treatment with tryptophane methylester hydrochloride employing a common peptide coupling procedure (DCC 1-HBT in DMF). 141 The resultant chiral cascade series was examined via ORD/CD and the preliminary data indicate a linear relationship between optical rotation and the number of surface tryptophane moieties. 

N-terminal pyroglutamyl, 6 Cys, 3 S-S) synthetic ent-Gurmarin (all D-amino acids) also blocks sweetness of sucrose, D-glucose L-glucose (at 1)... 

This similarity in spectral properties implies that haemocyanins should also have catalytic activity. From the available body of experimental data, it is clear that the distinction between the two major functions — oxygen transport and enzymatic activity — is determined by the presence or absence of a protein domain covering the active site. In the case of tyrosinase and catechol oxidase, inactive pro-enzyme forms are activated by removal of an amino acid which blocks the entrance channel to the active site (indicated by the black bar in Figure 14.7). Haemocyanins behave as silent inactive enzymes but can be activated in the same way if the blocking amino acid is removed. In arthropods, like crabs, this is located in the N-terminal domain of a subunit whereas in molluscs, like octopus, it is in the C-terminal domain of a functional unit. 

A newer method [26] switched to N-terminal (rather than C-terminal) attachment of the amino acid building blocks and to a base- (rather than an acid-) catalyzed cyclative cleavage strategy. In contrast to the first published method for the solid-phase synthesis of hydantoins [12], which relied on isocyanates for derivatiza-... 

Noradrenaline transporters (NAT) are localized in the presynaptic plasma membrane of adrenergic nerve terminals. They belong to a family of proteins with 12 putative transmembrane proteins which are responsible for recycling of released neurotransmitters (noradrena-line/adrenaline, dopamine, serotonin, amino acid transmitters) back into the presynaptic nerve ending. Noradrenaline transporters can be blocked by a number of different antidepressant drags, including tricyclic antidepressants (e.g. desipramine) and selective noradrenaline reuptake inhibitors (e.g. reboxetine). 

The removal of released DA from the synaptic extracellular space to facilitate its intraneuronal metabolism is achieved by a membrane transporter that controls the synaptic concentration. This transporter has been shown to be a 619 amino-acid protein with 12 hydrophobic membrane spanning domains (see Giros and Caron 1993). Although it has similar amino-acid sequences to that of the NA (and GABA) transporter, there are sufficient differences for it to show some specificity. Thus DA terminals will not concentrate NA and the DA transporter is blocked by a drug such as nomifensine which has less effect on NA uptake. Despite this selectivity some compounds, e.g. amphetamine and 6-OHDA (but not MPTP), can be taken up by both neurons. The role of blocking DA uptake in the central actions of cocaine and amphetamine is considered later (Chapter 23). 

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