1.Gas-phase ion-molecule reactions using regioselectively generated radical cations to model oxidative damage and probe radical sites in peptides.
Barlow CK1, Wright A, Easton CJ, O'Hair RA. Org Biomol Chem. 2011 May 21;9(10):3733-45. doi: 10.1039/c0ob01245a. Epub 2011 Mar 31.
Collision induced dissociation (CID) of sodiated peptide derivatives containing a nitrate ester functionality was used to regiospecifically generate three isomeric radicals of the model peptide Bz-Ala-Gly-OMe corresponding to radicals formed at: C(α) of the alanine residue [4+Na](+); C(α) of the glycine residue [5+Na](+); and the side chain of alanine [6+Na](+). The ion-molecule reactions of these peptide radicals were examined to model oxidative damage to peptides and to probe whether the radical sites maintain their integrity or whether they isomerise via intramolecular hydrogen atom transfer (HAT). Only [6+Na](+) is reactive towards O(2), forming the peroxyl radical [7+Na](+), which loses O(2), HO˙ and HO(2)˙ under CID. The radical ion [7 + Na](+) abstracts a hydrogen atom from 4-fluorothiophenol to form the hydroperoxide [8+Na](+), which upon CID fragments via the combined loss of HO˙ and CH(2)O. In contrast, all three of the isomeric sodiated radicals react with NO˙ and NO(2)˙ to form adducts.
2.Substrate specificity of honeydew melon protease D, a plant serine endopeptidase.
Yonezawa H1, Uchikoba T, Kaneda M. Biosci Biotechnol Biochem. 1997 Aug;61(8):1277-80.
The substrate specificity of honeydew melon (Cucumis melo var. inodorus Naud) protease D was studied by the use of synthetic substrates and oligopeptides derived from a protein hydrolyzate. The hydrolysis rates of succinyl-(L-Ala)1-3-p-nitroanilide (Suc-(Ala)1-3-pNA) the hydrolysis rate progressively rose in proportion to the increased chain length. Benzyloxycarbonyl-L-tyrosine p-nitrophenyl ester (Z-Tyr-ONp) and benzoyl-L-tyrosine ethyl ester (Bz-Tyr-OEt) were cleaved by honeydew melon protease D, but benzoyl-L-arginine p-nitroanilide (Bz-Arg-pNA), benzyloxycarbonyl-L-lysine p-nitrophenyl ester (Z-Lys-ONp) and tosyl-L-arginine methyl ester (Tos-Arg-OMe) were not hydrolyzed. Contrary to the results obtained by using synthetic substrates, the carboxyl sides of charged amino acid residues were preferentially cleaved by the enzyme in the oligopeptide substrates. The substrates that had charged or polar amino acids at P2 positions were not cleaved.
3.Mixed conformation in C alpha, alpha-disubstituted tripeptides: x-ray crystal structures of Z-Aib-Dph-Gly-OMe and Bz-Dph-Dph-Gly-OMe.
Pavone V1, Lombardi A, Saviano M, Di Blasio B, Nastri F, Fattorusso R, Zaccaro L, Maglio O, Yamada T, Omote Y, et al. Biopolymers. 1994 Dec;34(12):1595-604.
We report here the synthesis and molecular structure in the solid state of fully protected tripeptides containing C alpha, alpha-diphenylglycine (Dph), namely Z-Aib-Dph-Gly-OMe (Aib: C alpha, alpha-dimethylglycine) and Bz-Dph-Dph-Gly-OMe. The molecular conformation around the Dph residue, containing two bulky substituents, is fully extended, while the Aib residue, containing two smaller groups on the C alpha atom, adopts the typical 3(10)/alpha-helical conformation. Gly residues, without substituents on the C alpha atom, show different conformational preferences. Each residue seems to behave, from a conformational point of view, independently from the presence of the other residues, and thus mixed local conformations (folded and extended) are present in the crystals. The nonconventional peptide synthesis, using the Ugi reaction, is also reported.
4.Chloride-bridged oxovanadium(V) complexes with alkoxyalkoxide ligands. Synthesis, structure, electrochemistry and reactivities.
Rosenthal EC1, Cui H, Koch J, Escarpa Gaede P, Hummert M, Dechert S. Dalton Trans. 2005 Sep 21;(18):3108-17. Epub 2005 Jul 29.
A series of mixed alkoxyalkoxo chloro complexes of vanadium(V), [VOCl2(OCH2CH2OR)]2 (R = Me, Et, iPr, Bz), [VOCl2(OCMe2CH2OMe)]2 and [VOCl2(OCH2(cyclo-C4H7O)]2, were synthesised and characterised. The title compounds can be obtained either from VOCl3 and the alkoxyalcohols by HCl elimination or from the corresponding lithium alkoxides and VOCl3 by salt metathesis reaction. X-Ray diffraction studies revealed the title compounds to be dimers with chloride bridging ligands and intramolecular ether coordination. Electrochemical results obtained by cyclic voltammetry indicate irreversible, reductive behaviour. The interactions of the title compounds with oxygen, nitrogen and phosphorus donor ligands were examined. Phosphorus and nitrogen donors lead to reduction products whereas tetrahydrofuran coordinates to the vanadium(V) centre by breaking the chloride bridge. All tetrahydrofuran complexes, [VOCl2(OCH2CH2OR)(thf)] (R = Me, Et, iPr) and [VOCl2(OCMe2CH2OMe)(thf)], have been characterised by single-crystal X-ray diffraction.
