6tvj

<StructureSection load='6tvj' size='340' side='right'caption='[[6tvj]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[6tvj]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TVJ FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6tt6|6tt6]]</div></td></tr>

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== Publication Abstract from PubMed ==

Peptides are a rapidly growing class of therapeutics with various advantages over traditional small molecules, especially for targeting difficult protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing bioactive cyclic topologies that go beyond natural l-amino acids. Here, we report a generalizable framework that exploits the computational power of Rosetta, in terms of large-scale backbone sampling, side-chain composition and energy scoring, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we developed two new inhibitors (PD-i3 and PD-i6) of programmed cell death 1 (PD-1), a key immune checkpoint in oncology. A comprehensive biophysical evaluation was performed to assess their binding to PD-1 as well as their blocking effect on the endogenous PD-1/PD-L1 interaction. Finally, NMR elucidation of their in-solution structures confirmed our de novo design approach.

Target-templated de novo design of macrocyclic d-/l-peptides: discovery of drug-like inhibitors of PD-1.,Guardiola S, Varese M, Roig X, Sanchez-Navarro M, Garcia J, Giralt E Chem Sci. 2021 Mar 2;12(14):5164-5170. doi: 10.1039/d1sc01031j. PMID:34163753<ref>PMID:34163753</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6tvj" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Garcia, J]]

[[Category: Giralt, E]]

[[Category: Guardiola, S]]

[[Category: Varese, M]]

[[Category: Immunotherapy]]