Stability constants peptide complexes

Table 9. Stability constants of complex formation of cyclic peptides with alkali cations...

Keywords amino acids cadmium(II) peptides histidme cysteine thiolate ligands stability constants octahedral complexes polynuclear complexes... 

Because the stability constant of its complex with potassium is much greater than that with sodium, valinomycin is a relatively specific potassium ionophore. In contrast, the mushroom peptide antamanide has a binding cavity of a different geometry and shows a strong preference for sodium ions.388,390 The structure of the Na+-antamanide complex is also shown in Fig. 8-22B. The Streptomyces polyether antibiotic monensin (Fig. 8-22D),389,391 a popular additive to animal feeds, is also an ionophore. However, its mode of action, which involves disruption of Golgi functions, is uncertain 392... 

Stability constants for Cu11 complexation of Gly—X and X—Gly dipeptides show that even relatively small alkyl side chains can influence coordination. 3 At low pH, for example, the bidentate chelates N(amino),0(peptide) of L-Leu-Gly and L-Ile-Gly are the thermodynamically less stable, presumably due to steric hindrance from the branched side chains. Similar coordination by Gly—X is virtually independent of the nature of X. This latter result is not unexpected since only the Gly moiety is coordinating. However, on raising the solution pH (> 4) the peptide deprotonation that occurs to give tridentate N(amino),N(peptide),0(carboxyl) chelation is slightly inhibited by the Leu and lie residues (by 0.7-0.8 log units). 

The ability of this peptide to bind cations could be demonstrated by the upheld shift observed for the cation signals in the NMR spectrum on addition of a salt of, for example, the n-butyltrimethylammonium ion (BTMA+) to a solution of 2 in 0.2% d6-DMSO/CDCl3 [12]. This shift is a good indication of the interactions between the cation and 2, and it enabled us to determine a stability constant of 300 m 1 for the complex formed. The maximum chemical shift, Admax, observed for, for example, the N-methyl signal of the cation amounts to only —0.05 ppm, however, and is thus significantly smaller than the shift usually associated with com-... 

This table shows that, for a given anion, the stability constants of the 1 1 complexes of both peptides are comparable, and that the stability of the 1 1 complexes increases in the order Cl- > Br > I- > S042-. This order can be rationalized in terms of the size of the ions, with larger ions forming more stable complexes because they fit better into the available peptide cavity. For sulfate, an additional contribution to complex stability from the higher charge of this anion must be considered. 

The large stability constants K2 of the 2 1 complexes of 5 indicate that, once formed, the 1 1 complexes of this peptide have a strong tendency to bind the sec-... 

Tab. 2.2.3. Stability constants /

Intemasal delivery of peptide and protein drugs is severely restricted by pre-systemic elimination due to enz5miatic degradation or mucociliary clearance and by the limited extent of mucosal membrane permeability. a-CyD has been shown to remove some fatty acids from nasal mucosa and to enhance the nasal absorption of leuprolide acetate in rats and dogs. The utility of chemically modified CyDs as absorption enhancers for peptide drugs in rats has been demonstrated. For example, DM-P-CyD was shown to be a potent enhancer of insulin absorption in rats, and a minimal effective concentration of DM-(3-CyD for absorption enhancement exerted only a mild effect on the in vitro ciliary movement.The scope of interaction of insulin with CyDs is limited, because CyDs can only partially include the hydrophobic amino acid residues in peptides with small stability constants. Under in vivo conditions, these complexes will readily dissociate into separate components, and hence the displacement by membrane lipids may further destabilize the complexes. The direct interaction of peptides with CyDs is therefore of minor importance in the enhancement of nasal absorption. Of the hydrophilic CyDs tested, DM- 3-CyD had the most prominent inhibitory effect on the enzymatic degradation of both BLA and insulin in rat nasal tissue homogenates. Because of the limited interaction between peptides and CyDs,... 

Earlier studies established that imidazole coordination as part of a chelate structure requires the His residue to be near the amino end. This important positional feature of His is also apparent in the dipeptides Gly-His and His-Gly. As can be seen from Table 8 the His-Gly stability constants are invariably larger and the range of complexes formed also differs. Sundberg and Martin have reviewed the solution and solid state properties of His-containing peptides. More recently Gergely and his group have reexamined the coordinating properties of Gly-L-His, L-His-Gly and... 

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