Cleft-type receptors

Martin, M. Raposo, C. Almaraz. M. Crego. M. Caballero. C. Grande. M. Moran, J.R. Efficient recognition of chiral carbamoyl-a-hydroxyacids with a cleft-type receptor. Angew. Chem.,Int. Ed. Engl. 1996. 35 (20). 2386-2388. 

The blank flux of urea can not be neglected (Jbiank == 4.4 x 10 mol m s, and the assisted flux was obtained by substraction of the blank flux from the measured flux. The model has been applied for the transport of urea using two types of carriers, e,g. lipophilic metallomacrocycles 15 and 16 69), and polyaza (cleft-type) receptors 17, 18, and 19 71), The transport data are presented in Table 9. Transport experiments were carried out by varying the urea concentration to obtain and In Figure 18, the assisted flux is plotted vs. the initial urea concentration for carrier 15. Diffusion constants and extraction constants for macrocycles 15 and 16 are also given in Table 9. 

Figure 17.1. Neurotransmission (specific case of peptidergic cells). Production of the peptides in the cel I body (1). Packing of the peptides i nto large dense core vesicles for further transport to the axons (2). Release of neuropeptides from the cell soma (3) dendrites (4) and outside of the synapse (5). Release of classic neurotransmitters in the synaptic cleft (6). G-protein-coupled type receptors, which act as peptide receptors. (See color insert.)...

On the basis of this cleft-type scaffold, Anslyn s group prepared a chemo-sensor library to discover a sophisticated nucleotide receptor possessing high selectivity toward ATP [32]. The attachment of the scaffold on Wang resin for solid phase synthesis, followed by tethering two tripeptide chains branch-... 

Still and coworkers prepared the highly selective, D2-synnnetric receptor 37 for amino acids and small peptides by simple condensation of (/ , )-cyclohexane-1,2-diamihe and trimesic acid. ° Complexes are held together by four intermolecular hydrogen bonds and resemble a peptidic three-strand (1-sheet. A further, enantiomer-discriminating interaction is based on steric complementarity between the amino acid side chain and the cleft-type cavity of the receptor. 

Homanics, G. E., Delorey, T. M Firestone, L. L., et al. (1997) Mice devoid of y-aminobu-tyrate type A receptor p3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc. Natl. Acad. Sci. USA 94,4143-4148. 

M. (1995) Deficiency of the P3 subunit of the type A y-aminobutyric acid receptor causes cleft palate in mice. Nature Genetics 11, 344-346. 

The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane. 

Each neuron usually releases only one type of neurotransmitter. Neurons that release dopamine are referred to as dopaminergic, for example, while those that release acetylcholine are cholinergic, etc. The transmitters that are released diffuse through the synaptic cleft and bind on the other side to receptors on the postsynaptic membrane. These receptors are integral membrane proteins that have binding sites for neurotransmitters on their exterior (see p. 224). 

Thus, for small SA molecules, the actual binding domains of a macromolecule type SO could be multiple, but not necessarily homogeneous. They can be expressed as cavities, clefts, pockets or bay areas as described for receptor-type proteins. 

In the presynaptic cell, the neurotransmitters are stored in vesicles. On arrival of an electrical signal (action potential, see 16.2), an influx of Ca takes place into the presynaptic cell as voltage-gated Ca channels are opened. The increase in Ca concentration leads to fusion of the vesicles with the membrane of the postsynaptic cell. The neurotransmitters are released into the synaptic cleft and diffuse to a corresponding receptor on the surface of the postsynaptic cell. Binding of the nemotransmitter to the receptor induces opening of an ion channel that is a component of the receptor. The type of ions that can enter depends on the selectivity of the ion channel. There are Na K, Ca and Cf specific ion channels. The ion flux creates an electric signal in the post-... 

Complexation experiments show that compounds of type 2 are good receptors for dihydroxybenzenes, as expected [11]. Two types of interaction-hydrogen bonding and n-n stacking interactions - cooperate to bind a guest molecule in the cleft of the clip. Association constants for 3 and 5-7 with dihydroxy-substituted aromatic compounds were determined using H-NMR titrations in CHCI3 (Table 1). The role of n-n interactions is evident from the difference in... 

M3 has two domains an N-terminal domain and a G-terminal domain, each composed of elaborated / -sandwiches with closest structural homologies to the G-terminal receptor binding domain of diptheria toxin, and the V-type Ig-fold, respectively. It exits in solution as a head to tail dimer, which leads to the formation of a cleft between the N-terminal domain of one subunit and the G-terminal domain of the other. Ghemokines bind within each cleft, thus forming a 2 2 complex. Figure lOA shows a surface... 

HT in synaptic clefts are therefore presumed to lead to changes in pain thresholds and induce antinociception. A recent study, by using the formalin test in rats, attempted to determine the identity and possible localization of the receptor sub-types predominantly involved in the antinociceptive effects of antidepressants. Thus, it has been shown that ICV administration of 5-HT2 and 5-HT3-receptor antagonists inhibited the antinociceptive potency of serotonin-reuptake inhibitors (Yokogawa et al., 2002). 

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