No abstract

A comparative study of syn vs anti carboxylic acids in hybrid peptides based on experimental electron density studies and theoretical calculations shows that, in the anti form, all three bond angles surrounding C of the -COOH group are close to ∼120°, as expected for a C-sp atom, whereas in the syn form, the ∠C-C(O)-O angle is significantly smaller by 5-10°. The oxygen atom in the carboxyl group is more electronegative in the anti form, so the polarity of the acidic O-H bond is higher in the anti form compared to the syn form, as observed within the limitations of H atom treatment in X-ray diffraction. Consequently, the investigated anti carboxylic acid forms the strongest O-H···O hydrogen bond among all model compounds. Furthermore, according to natural bond orbital analysis, the oxygen lone pairs are clearly nonequivalent, as opposed to the general notion of hybridization of equivalent sp and sp lone pairs on carbonyl or hydroxyl oxygen atoms. The hybridization of the lone pairs is directly related to the directionality and strength of hydrogen bonds.

Conopressin, a nonapeptide disulfide CFIRNCPKG amide present in cone snail venom, undergoes a facile cleavage at the Cys6−Pro7 peptide bond to yield a disulfide bridged b 6 ion. Analysis of the mass spectral fragmentation pattern reveals the presence of a major fragment ion, which is unambiguously assigned as the tripeptide sequence IRN amide. The sequence dependence of this unusual fragmentation process has been investigated by comparing it with the fragmentation patterns of related peptides, oxytocin (CYIQNCPLG amide), Lys-vasopressin (CYFQNCPKG amide), and a series of synthetic analogues. The results establish the role of the Arg4 residue in facilitating the unusual N−C α bond cleavage at Cys6. Structures are proposed for a modified disulfide bridged fragment containing the Cys1 and Cys6 residues. Gas-phase molecular dynamics simulations provide evidence for the occurrence of conformational states that permit close approach of the Arg4 side chain to the Cys6 C β methylene protons.