Lead complexes peptides

The cyclopeptide described above was tailored to form stable potassium complexes. It is one of the very few examples of complex peptide syntheses which do not lead to a natural compound. 

Structural characterization of NRPSs has yielded significant insight into the enzymology of these complex biosynthetic machines and has provided a framework for engineering these systems toward novel function. As summarized in this section, X-ray crystal and NMR structures have been determined for both individual NRPS domains and multidomain constructs. Overall, these studies support a monomeric structure for NRPS assembly line units where significant domain motion is necessary to allow participation of the various active sites in the chemistry leading to peptide products. 

Salt induced peptide formation [108] is based on a dehydrating activity of concentrated NaCl solutions in which free water molecules are less available, which drives the equilibrium towards peptide formation. This change in the thermodynamic barrier is coupled to a decrease of the kinetic barrier owing to the addition of a Cu(II) salt catalyst. A complex of copper with two amino acid ligands 14 has been proposed to be responsible for the catalytic process. In this way, the reaction between two amino acid ligands leading to peptide bond formation can take place intramolecularly ... 

Fig. 6.5 Possible interaction between the helical dinuclear Zn(ll)-peptide [33] and DNA which leads to hydrolytic cleavage of the phosphate bond. The structure of the Zn(ll)-ATANP complex is shown in the top right-hand corner...

Figure 12.2 A hypothetical synapse where co-existence of peptides and classical transmitters occurs. A is a classical transmitter whereas B and C are peptides. The slow synthesis of peptides and the need for axonal transport may mean that in active neurons, the classical transmitter may be released under all conditions, but the peptide(s) may require higher intensities of stimulation for release and be depleted if the neuron continues to fire for long periods. Competition for peptidases can lead to changes in levels of two co-released peptides. At the postsynaptic site, the receptor mechanisms of the co-existing transmitters can also produce complex changes in neuronal activity...

The triptans are considered specific therapies in that they target the pathophysiology underlying migraine.33 They abort headache through beneficial effects on neuronal imbalances.11 Triptans inhibit neurotransmission in the trigeminal complex and activate serotonin lb/Id pathways that modulate nociception in the brain stem. They also decrease the release of vasoactive peptides leading to vascular reactivity and pain.34 Triptans are a welcome addition to the therapeutic armamentarium in that they are available in intranasal, subcutaneous, and oral... 

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