17O NMR and FT-IR study of the ionization state of peptides in aprotic solvents Application to Leu-enkephalin

AbstractThe ionization state of Leu-enkephalin in DMSO and MeCN/DMSO (4/1) solution was studied by the combined use of 17O NMR and FT-IR spectroscopy. After lyophilization or an aqueous solution at nearly neutral pH, Leu-enkephalin essentially exists in the uncharged state in MeCN/DMSO (4/1) solution. In pure DMSO, only 40% of the Leu-enkephalin molecules are in the zwitterionic state under the same conditions

Physical Activity and Natural Anti-VIP Antibodies: Potential Role in Breast and Prostate Cancer Therapy

BACKGROUND: There is convincing evidence from numerous clinical and epidemiological studies that physical activity can reduce the risk for breast and prostate cancer. The biological mechanisms underlying this phenomenon remain elusive. Herein we suggest a role for naturally produced antibodies reactive with the vasoactive intestinal peptide (VIP) in the suppression of breast and prostate cancer, which we believe could offer a possible molecular mechanism underlying control of these cancers by physical exercise. METHODOLOGY AND RESULTS: We found that sera from individuals having breast and prostate cancers have decreased titers of VIP natural antibodies as demonstrated by a lower reactivity against peptide NTM1, having similar informational and structural properties as VIP. In contrast, sera collected from elite athletes, exhibited titers of natural NTM1-reactive antibodies that are significantly increased, suggesting that physical activity boosts production of these antibodies. SIGNIFICANCE: Presented results suggest that physical exercise stimulates production of natural anti-VIP antibodies and likely results in suppression of VIP. This, in turn, may play a protective role against breast and prostate cancers. Physical exercise should be further investigated as a potential tool in the treatment of these diseases

A new helicoid-type sequential oligopeptide carrier (SOC(n)) for developing potent antigens and immunogens

A new class of sequential oligopeptide carriers (SOC(n)) for anchoring antigenic/immunogenic peptides has been constructed. The carrier, formed by the repetitive Lys-Aib-Gly moiety, is designed to display a predetermined 3D structure, so that the attached peptides would obtain a defined spatial orientation. Conformational analysis showed that SOC(n) adopt a distorted 310-helical structure, while the coupled peptides preserve their original 'active' structure. Coupling to the carrier may also result to the enhancement of one conformer of the anchored peptide. It is concluded that the structure of SOC(n) offers an optimal presentation of the attached peptides, so that potent antigens or immunogens are generated. Copyright (C) 1999 Elsevier Science Ltd

Structural, molecular and immunological properties of linear B-cell epitopes of Ro60KD autoantigen

Antibodies to Ro60KD protein are found with high frequency in sera from patients with systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS). Two major epitopes of the Ro60KD antigen, the TKYKQRNGWSHKDLLRSHLKP (169-190) and the ELYKEKALSVETEKLLKYLEAV (211-232), were synthesized and their antigenic and structural properties were studied. Using a large panel of SLE and pSS patients' sera, it was found that the anti-Ro60KD reactivity of both Ro60KD epitopes is rather limited (≃45%), although they retain their original disease specificity. The epitope p.169- 190 possessed sequence similarity with the peptide RPDAEYWNSQKDLLEQKRGR, shared in the β-chain of different HLA-DR molecules, among them the HLA-DR3 (which is associated with anti-Ro/Sjogren's syndrome A (SSA) response in patients with SLE). The antigenicity of the HLA-DR3 RPDAEYWNSQKDLLEQKRGR peptide was found to be similar to the 169-190 homologous Ro60KD epitope, recognized mainly by SLE sera. Structural studies showed that the 211-232 Ro60KD epitope exhibits pronounced helical characteristics, while the 169- 190 epitope and the HLA-DR3 homologous peptide possess a somewhat lower percentage of α-helix. A β-folded structure was identified in the latter two peptides. Although the diagnostic value of the reported Ro60KD epitopes seems to be rather limited, correlations with other ribonucleoprotein epitopes (La/Sjogren's syndrome B, Ro52KD) may prove complementary to each other and valuable in clinical use. The ordered structure of the HLA-DR3 homologous peptide, exposed to the autoantibody binding, may offer an initiative in further investigation of the role of the HLA haplotypes, associated with the anti-Ro/SSA response, in the autoimmune stimulus