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We are pleased to open registration for the next PPSG webinar held at 1 pm (UK time) on 3^rd July 2026.听The next scientists presenting will be Dr Andre Cobb (King鈥檚 College London) and Dr Anne Conibear (Tu Wien).

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Dr Andre Cobb

Professor of Organic Chemistry at King鈥檚 College London

听鈥�Synthesis of Peptidic 伪,未-Foldamers and their Application to Catalysis鈥�

听Nature has selected folded linear polymers to carry out its most elaborate functions. For example, proteins and peptides are ostensibly linear systems, but fold into more complex structures, leading to a specific arrangement of the associated side chains and thus dictating the ultimate function. This complex relationship between the structure of the biopolymer and its activity has inspired chemists to develop their own unnatural oligomers with strong and predictable folding properties, known as 鈥渇oldamers鈥� with the long-term goal of creating artificial folded architectures that will not only equal the abilities of biopolymers, but surpass them. The distinctive advantages that a foldamer can bring over biological molecules include novel functionality, smaller size and greater biostability. We have developed a hybrid peptidic foldamer consisting of 伪- and 未-residues (which we access via organocatalytic methodology) in a 1:1 ratio that forms a stable 13/11-helix. We describe both the solid and solution phase synthetic approaches to these systems and demonstrate that two of the 伪-residues are close enough to participate in bifunctional catalysis. We describe the current state of our investigations into this unique system.

References:

[1] Nodes, W. J.; Nutt, D. R.; Chippindale, A. M.; Cobb, A. J. A., J. Am. Chem. Soc. 131, 16016 (2009).

[2] Fanelli, R.; Berta, D.; F枚ldes, T.; Rosta, E.; Atkinson, R. A.; Hofmann, H.-J.; Shankland, K.; Cobb, A. J. A., J. Am. Chem. Soc., 132, 1382. (2020)

[3] Lin, Q.; Lan, H.; Ma, C.; Stendall, R. T.; Shankland, K.; Musgrave, R. A.; Horton, P. N.; Baldauf, C.; Hofmann, H.-J.; Butts, C. P.; M眉ller, M. M.; Cobb, A. J. A., Angew. Chem. Int. Ed., e202305326 (2023)

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Dr Anne Conibear

Assistant Professor at the TU Wien

鈥�Post-translational Modifications of Disordered Proteins鈥�

The conformational flexibility of intrinsically disordered proteins and protein regions (IDRs), and their accessibility to modifying enzymes make IDRs hot-spots for protein regulation by posttranslational modifications (PTMs). Such PTMs increase the complexity of the proteome and can have central roles in regulating protein function, location, interactions and degradation. Little is known, however, about how PTMs modulate the conformations and interactions of IDRs, as they typically occupy multiple conformational states, have promiscuous interactions, and are often removed or poorly represented in structural biology studies. In this presentation, I will discuss our work towards understanding how PTMs modulate the conformations and interactions of IDRs. Protein synthesis and semi-synthesis provides access to site-specifically modified variants of IDRs, such as the HMGN1 and Tau proteins, and disordered termini of Hsp90 and 尾-catenin. These protein variants enable us to study the precise effects of PTMs and cross-talk of multiple PTMs on conformational populations using NMR spectroscopy. With these examples, I aim to show how integrating chemical protein synthesis with structural biology of IDRs allows us to gain new insights into the effects of PTMs on the conformation, dynamics and regulation of IDRs.

References:

[1] Conibear, A. C., Nat. Rev. Chem. 4, 674-695 (2020).

[2] Niederacher, G., Urwin, D.; Dijkwel, Y., Tremethick, D. J., Rosengren, K. J., Becker, C. F. W., Conibear, A. C., RSC Chem. Biol. 2, 537-550 (2021).

[3] Iebed, D., G枚kler, T., van Ingen, H., Conibear, A. C., ChemBioChem, 25, e20241023 (2024).

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