7w8r
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7w8r]] 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=7W8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W8R FirstGlance]. <br> | <table><tr><td colspan='2'>[[7w8r]] 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=7W8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W8R FirstGlance]. <br> | ||
| - | </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=7w8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w8r OCA], [https://pdbe.org/7w8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w8r RCSB], [https://www.ebi.ac.uk/pdbsum/7w8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w8r ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</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=7w8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w8r OCA], [https://pdbe.org/7w8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w8r RCSB], [https://www.ebi.ac.uk/pdbsum/7w8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w8r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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Peptides constrained through multiple disulfides (or disulfide-rich peptides, DRPs) have been an emerging frontier for ligand and drug discovery. Such peptides have the potential to combine the binding capability of biologics with the stability and bioavailability of smaller molecules. However, DRPs with stable three-dimensional (3D) structures are usually of natural origin or engineered from natural ones. Here, we report the discovery and identification of CPPC (cysteine-proline-proline-cysteine) motif-directed DRPs with stable 3D structures (i.e., CPPC-DRPs). A range of new CPPC-DRPs were designed or selected from either random or structure-convergent peptide libraries. Thus, for the first time we revealed that the CPPC-DRPs can maintain diverse 3D structures by taking advantage of constraints from unique dimeric CPPC mini-loops, including irregular structures and regular alpha-helix and beta-sheet folds. New CPPC-DRPs that can specifically bind the receptors (CD28) on the cell surface were also successfully discovered and identified using our DRP-discovery platform. Overall, this study provides the basis for accessing an unconventional peptide structure space previously inaccessible by natural DRPs and computational designs, inspiring the development of new peptide ligands and therapeutics. | Peptides constrained through multiple disulfides (or disulfide-rich peptides, DRPs) have been an emerging frontier for ligand and drug discovery. Such peptides have the potential to combine the binding capability of biologics with the stability and bioavailability of smaller molecules. However, DRPs with stable three-dimensional (3D) structures are usually of natural origin or engineered from natural ones. Here, we report the discovery and identification of CPPC (cysteine-proline-proline-cysteine) motif-directed DRPs with stable 3D structures (i.e., CPPC-DRPs). A range of new CPPC-DRPs were designed or selected from either random or structure-convergent peptide libraries. Thus, for the first time we revealed that the CPPC-DRPs can maintain diverse 3D structures by taking advantage of constraints from unique dimeric CPPC mini-loops, including irregular structures and regular alpha-helix and beta-sheet folds. New CPPC-DRPs that can specifically bind the receptors (CD28) on the cell surface were also successfully discovered and identified using our DRP-discovery platform. Overall, this study provides the basis for accessing an unconventional peptide structure space previously inaccessible by natural DRPs and computational designs, inspiring the development of new peptide ligands and therapeutics. | ||
| - | Structure-guided design of CPPC-paired disulfide-rich peptide libraries for ligand and drug discovery.,Wu Y, Fan S, Dong M, Li J, Kong C, Zhuang J, Meng X, Lu S, Zhao Y, Wu C Chem Sci. 2022 May 20;13(26):7780-7789. doi: 10.1039/d2sc00924b. eCollection 2022, Jul 6. PMID:35865895<ref>PMID:35865895</ref> | + | Structure-guided design of CPPC-paired disulfide-rich peptide libraries for ligand and drug discovery.,Wu Y, Fan S, Dong M, Li J, Kong C, Zhuang J, Meng X, Lu S, Zhao Y, Wu C Chem Sci. 2022 May 20;13(26):7780-7789. doi: 10.1039/d2sc00924b. eCollection 2022 , Jul 6. PMID:35865895<ref>PMID:35865895</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Solution structures of a disulfide-rich peptide that can bind mdm2
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