Ligand-peptide complexation

Fig. 8. Lck SH2 domain-peptide complex (Ac-cmF-Glu-Glu-Ile-OH, 12) revealing the twopronged plug engaging a two-holed socket 1 binding mode, reminiscent of the majority of SH2 domains (Protein Databank entry code 1BHF.PDB [118]). The protein is depicted in a Connolly surface mode, the ligand is given in a ball-and-stick representation. The cmF residue is deeply buried in its binding pocket (left)...

The Novartis group used the X-ray structure of a Grb2-peptide complex [68] as the structural basis for a design attempt that yielded entirely new non-peptide SH2 domain ligands [164]. As mentioned several times throughout this contribution, the interaction of the pTyr sidechain and the Asn sidechain in pTyr+2 position of the peptide ligand have been identified as key elements for molecular recognition (see Fig. 10). The obvious relevance of these two sidechain functionalities allowed the definition of a minimal pharmacophore pattern that... 

The kinetics and mechanisms of substitution reactions of metal complexes are discussed with emphasis on factors affecting the reactions of chelates and multidentate ligands. Evidence for associative mechanisms is reviewed. The substitution behavior of copper(III) and nickel(III) complexes is presented. Factors affecting the formation and dissociation rates of chelates are considered along with proton-transfer and nucleophilic substitution reactions of metal peptide complexes. The rate constants for the replacement of tripeptides from copper(II) by triethylene-... 

Fig. 2 A 1. 8-A resolution sigma-weighted (IFg-Fc) map of the octapeptide, contoured at la level. B Stereo view of the superimposed positions of the peptide [80] and carbohydrate [82] ligands. Atom types are the same as in Fig. 1. The ordered solvent (water) molecules (S) associated with the peptide complex are also shown. The solvent molecules S2, S9 and Si and the residue Rha C are shown to occupy a similar area of the site, the deep pocket of the combining site groove (see also Fig. 1). Reproduced from [80]. 2003 by The National Academy of Sciences of the USA...

The other simple peptide complex e.g. [Fe(Z-Cys-Ala-OMe)4]2- did not exhibit such a reversible redox couple under similar conditions. The Fe(lll) complexes of simple peptide thiolates or cysteine alkyl esters are found to be thermally quite unstable and decompose by oxidaticxi at the thiolate ligand by intramolecular electron transfer. Thus the macro-ring chelation of the Cys-Pro-Leu-Cys ligand appears to stabilize the Fe(in) state. The stability of the Fe(ni) form as indicated by the cyclic voltamnoogram measurements and by the visible spectra of the Fe(in) peptide complexes suggests that the peptide prevents thermal and hydrolytic decomposition of the Fe-S bond because of the hydrophobicity and steric bulk of the Pro and Leu residues (3,4). 

Protein-Ligand Interactions Exchange processes and determination of ligand conformation and protein-ligand contacts, 238, 657 nuclear magnetic studies of protein-peptide complexes,... 

With the above-mentioned variety of addition reactions based on the addition-elimination mechanism almost any functional group or molecule can be attached to CgQ. Some examples are acetylenes [43, 52], peptides [53], DNA-fragments [53], polymers [54], macrocycles [55, 56], porphyrins [56, 57], dendrimers [58-60] or ligands for complex formation [56], Cjq can be turned into hybrids that are biologically active, water soluble, amphiphilic or mixable with polymers [53-55, 58, 61-69],... 

The observation (112-115) that neutral aqueous solutions of [Ni11H 3G4]2 consume molecular oxygen with the appearance of a strongly absorbing transient at 350 nm lead to detailed investigations and discovery of nickel(III)-peptide complexes (113). The oxidized nickel complexes have absorption maxima around 325 and 240 nm (e = 5240 and 11,000 M I cm-1, respectively for [NiM1H 3G4]-). Reduction potentials (116) (Table II), measured by cyclic voltammetry, show a small dependence on ligand structure which can be correlated... 

Nucleophilic reactions, in particular ligand replacement by EDTA and polyamine ligands, readily occur with Ni and Cu11 peptide complexes, the most reactive nucleophiles being those that contain an amine group to give an associative-type intermediate. The presence of histidine as the third residue in a peptide appears to reduce the susceptibility of Cu complexes to nucleophilic attack. 

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