View source for 8cun


==Solution NMR structure of 8-residue Rosetta-designed cyclic peptide D8.21 in 50% d6-DMSO and 50% water with cis/trans switching (CC conformation, 50%)==
<StructureSection load='8cun' size='340' side='right'caption='[[8cun]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cun]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CUN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cun OCA], [https://pdbe.org/8cun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cun RCSB], [https://www.ebi.ac.uk/pdbsum/8cun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cun ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
We use computational design coupled with experimental characterization to systematically investigate the design principles for macrocycle membrane permeability and oral bioavailability. We designed 184 6-12 residue macrocycles with a wide range of predicted structures containing noncanonical backbone modifications and experimentally determined structures of 35; 29 are very close to the computational models. With such control, we show that membrane permeability can be systematically achieved by ensuring all amide (NH) groups are engaged in internal hydrogen bonding interactions. 84 designs over the 6-12 residue size range cross membranes with an apparent permeability greater than 1 x 10(-6) cm/s. Designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to robustly design membrane-permeable and orally bioavailable peptides with high structural accuracy should contribute to the next generation of designed macrocycle therapeutics.

Accurate de novo design of membrane-traversing macrocycles.,Bhardwaj G, O'Connor J, Rettie S, Huang YH, Ramelot TA, Mulligan VK, Alpkilic GG, Palmer J, Bera AK, Bick MJ, Di Piazza M, Li X, Hosseinzadeh P, Craven TW, Tejero R, Lauko A, Choi R, Glynn C, Dong L, Griffin R, van Voorhis WC, Rodriguez J, Stewart L, Montelione GT, Craik D, Baker D Cell. 2022 Sep 15;185(19):3520-3532.e26. doi: 10.1016/j.cell.2022.07.019. Epub , 2022 Aug 29. PMID:36041435<ref>PMID:36041435</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cun" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Montelione GT]]
[[Category: Ramelot TA]]
[[Category: Tejero R]]