8dpy
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 5: | Line 5: | ||
<table><tr><td colspan='2'>[[8dpy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPY FirstGlance]. <br> | <table><tr><td colspan='2'>[[8dpy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPY FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T7C:3-({2-[(2-amino-2-oxoethyl)amino]ethyl}sulfanyl)propanoic+acid'>T7C</scene>, <scene name='pdbligand=T7H:3- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T7C:3-({2-[(2-amino-2-oxoethyl)amino]ethyl}sulfanyl)propanoic+acid'>T7C</scene>, <scene name='pdbligand=T7H:3-[2-(2-hydroxy-2-oxoethylamino)ethylsulfanyl]propanoic+acid'>T7H</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=8dpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpy OCA], [https://pdbe.org/8dpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpy RCSB], [https://www.ebi.ac.uk/pdbsum/8dpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpy ProSAT]</span></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=8dpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpy OCA], [https://pdbe.org/8dpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpy RCSB], [https://www.ebi.ac.uk/pdbsum/8dpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | Mimics of protein secondary and tertiary structure offer rationally-designed inhibitors of biomolecular interactions. beta-Sheet mimics have a storied history in bioorganic chemistry and are typically designed with synthetic or natural turn segments. We hypothesized that replacement of terminal inter-beta-strand hydrogen bonds with hydrogen bond surrogates (HBS) may lead to conformationally-defined macrocyclic beta-sheets without the requirement for natural or synthetic beta-turns, thereby providing a minimal mimic of protein beta- | + | Mimics of protein secondary and tertiary structure offer rationally-designed inhibitors of biomolecular interactions. beta-Sheet mimics have a storied history in bioorganic chemistry and are typically designed with synthetic or natural turn segments. We hypothesized that replacement of terminal inter-beta-strand hydrogen bonds with hydrogen bond surrogates (HBS) may lead to conformationally-defined macrocyclic beta-sheets without the requirement for natural or synthetic beta-turns, thereby providing a minimal mimic of a protein beta-sheet. To access turn-less antiparallel beta-sheet mimics, we developed a facile solid phase synthesis protocol. We surveyed a dataset of protein beta-sheets for naturally observed interstrand side chain interactions. This bioinformatics survey highlighted an over-abundance of aromatic-aromatic, cation-pi and ionic interactions in beta-sheets. In correspondence with natural beta-sheets, we find that minimal HBS mimics show robust beta-sheet formation when specific amino acid residue pairings are incorporated. In isolated beta-sheets, aromatic interactions endow superior conformational stability over ionic or cation-pi interactions. Circular dichroism and NMR spectroscopies, along with high-resolution X-ray crystallography, support our design principles. |
| - | Macrocyclic beta-Sheets Stabilized by Hydrogen Bond Surrogates.,Nazzaro A, Lu B, Sawyer N, Watkins AM, Arora PS Angew Chem Int Ed Engl. 2023 | + | Macrocyclic beta-Sheets Stabilized by Hydrogen Bond Surrogates.,Nazzaro A, Lu B, Sawyer N, Watkins AM, Arora PS Angew Chem Int Ed Engl. 2023 Oct 9;62(41):e202303943. doi: , 10.1002/anie.202303943. Epub 2023 Jun 2. PMID:37170337<ref>PMID:37170337</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
Synthetic Beta Sheet Macrocycle Stabilized by Hydrogen Bond Surrogates
| |||||||||||
