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6. Natural products in drug discovery: advances and opportunities

Author

Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., Orhan, I. E., Banach, M., Rollinger, J. M., Barreca, D., Weckwerth, W., Bauer, R., Bayer, E. A., Majeed, M., Bishayee, A., Bochkov, V., Bonn, G. K., Braidy, N., Bucar, F., Cifuentes, A., D'Onofrio, G., Bodkin, M., Diederich, M., Dinkova-Kostova, A. T., Efferth, T., El Bairi, K., Arkells, N., Fan, T. -P., Fiebich, B. L., Freissmuth, M., Georgiev, M. I., Gibbons, S., Godfrey, K. M., Gruber, C. W., Heer, J., Huber, L. A., Ibanez, E., Kijjoa, A., Kiss, A. K., Lu, A., Macias, F. A., Miller, M. J. S., Mocan, A., Muller, R., Nicoletti, F., Perry, G., Pittala, V., Rastrelli, L., Ristow, M., Russo, G. L., Silva, A. S., Schuster, D., Sheridan, H., Skalicka-Wozniak, K., Skaltsounis, L., Sobarzo-Sanchez, E., Bredt, D. S., Stuppner, H., Sureda, A., Tzvetkov, N. T., Vacca, R. A., Aggarwal, B. B., Battino, M., Giampieri, F., Wink, M., Wolfender, J. -L., Xiao, J., Yeung, A. W. K., Lizard, G., Popp, M. A., Heinrich, M., Berindan-Neagoe, I., Stadler, M., Daglia, M., Verpoorte, R., Supuran, C. T., Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., Orhan, I. E., Banach, M., Rollinger, J. M., Barreca, D., Weckwerth, W., Bauer, R., Bayer, E. A., Majeed, M., Bishayee, A., Bochkov, V., Bonn, G. K., Braidy, N., Bucar, F., Cifuentes, A., D'Onofrio, G., Bodkin, M., Diederich, M., Dinkova-Kostova, A. T., Efferth, T., El Bairi, K., Arkells, N., Fan, T. -P., Fiebich, B. L., Freissmuth, M., Georgiev, M. I., Gibbons, S., Godfrey, K. M., Gruber, C. W., Heer, J., Huber, L. A., Ibanez, E., Kijjoa, A., Kiss, A. K., Lu, A., Macias, F. A., Miller, M. J. S., Mocan, A., Muller, R., Nicoletti, F., Perry, G., Pittala, V., Rastrelli, L., Ristow, M., Russo, G. L., Silva, A. S., Schuster, D., Sheridan, H., Skalicka-Wozniak, K., Skaltsounis, L., Sobarzo-Sanchez, E., Bredt, D. S., Stuppner, H., Sureda, A., Tzvetkov, N. T., Vacca, R. A., Aggarwal, B. B., Battino, M., Giampieri, F., Wink, M., Wolfender, J. -L., Xiao, J., Yeung, A. W. K., Lizard, G., Popp, M. A., Heinrich, M., Berindan-Neagoe, I., Stadler, M., Daglia, M., Verpoorte, R., and Supuran, C. T.

Subjects
0301 basic medicine, Engineering, Drug Industry, Review Article, Communicable Diseases, Natural (archaeology), 03 medical and health sciences, 0302 clinical medicine, Transferases, Neoplasms, Drug Discovery, Humans, Pharmaceutical industry, Pharmacology, Biological Products, Natural products, Genome, business.industry, Drug discovery, General Medicine, Chemical biology, 030104 developmental biology, Risk analysis (engineering), 030220 oncology & carcinogenesis, Genome mining, business
Abstract

The International Natural Product Sciences Taskforce: et al., Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities., A.C. and E.I. thank the Ministerio de Ciencia, Innovación y Universidades, Spain (Project AGL2017-89417-R) for support. F.A.M. acknowledges the support by Ministerio de Economia y Competitividad, Spain (project AGL2017-88083-R).

Published
2021
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38. Effect of the chain mobility of polymeric reversed-phase stationary phases on polypeptide retention

Author

Hanson, Michael, Unger, Klaus K., Schmid, Jutta, Albert, Klaus, and Bayer, E.

Subjects
Polypeptides -- Research, Chromatography -- Research, Protein folding -- Research, Chemistry
Abstract

The resolution of polypeptides in reversed-phase chromatography can be improved by inducing conformational changes in the solute. Protein unfolding can be achieved by an increased accessability of the hydrophobic stationary phase. We elucidated how far results from CP/MAS solid-state NMR relaxation measurements could be correlated with chromatographic data in terms of protein and peptide retention. The retentivity and denaturation potential of reversed stationary phases is controlled not only by their hydrophobicity but also by their ligand mobility and steric properties. As a consequence, we developed a simplified model for protein retention on stationary phases with different dynamic properties: We used an n-octadecyl phase (RP18), a poly(octadecyl methacrylate) phase (POMA), and a polybutadiene phase (PBD).

Published
1993

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