View source for 6cg3


==Macrocyclic peptide derived from Abeta(17-36) - (ORN)LV(PHI)FAED(ORN)AII(2-nitrobenzylglycine)L(ORN)V==
<StructureSection load='6cg3' size='340' side='right'caption='[[6cg3]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cg3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CG3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CG3 FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=EZY:'>EZY</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cg3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cg3 OCA], [http://pdbe.org/6cg3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cg3 RCSB], [http://www.ebi.ac.uk/pdbsum/6cg3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cg3 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
A key challenge in studying the biological and biophysical properties of amyloid-forming peptides is that they assemble to form heterogeneous mixtures of soluble oligomers and insoluble fibrils. Photolabile protecting groups have emerged as tools to control the properties of biomolecules with light. Blocking intermolecular hydrogen bonds that stabilize amyloid oligomers provides a general strategy to control the biological and biophysical properties of amyloid-forming peptides. In this paper we describe the design, synthesis, and characterization of macrocyclic beta-hairpin peptides that are derived from amyloidogenic peptides and contain the N-2-nitrobenzyl photolabile protecting group. Each peptide contains two heptapeptide segments from Abeta16-36 or Abeta17-36 constrained into beta-hairpins. The N-2-nitrobenzyl group is appended to the amide backbone of Gly33 to disrupt the oligomerization of the peptides by disrupting intermolecular hydrogen bonds. X-ray crystallography reveals that N-2-nitrobenzyl groups can either block assembly into discrete oligomers or permit formation of trimers, hexamers, and dodecamers. Photolysis of the N-2-nitrobenzyl groups with long-wave UV light unmasks the amide backbone and alters the assembly and the biological properties of the macrocyclic beta-hairpin peptides. SDS-PAGE studies show that removing the N-2-nitrobenzyl groups alters the assembly of the peptides. MTT conversion and LDH release assays show that decaging the peptides induces cytotoxicity. Circular dichroism studies and dye leakage assays with liposomes reveal that decaging modulates interactions of the peptides with lipid bilayers. Collectively, these studies demonstrate that incorporating N-2-nitrobenzyl groups into macrocyclic beta-hairpin peptides provides a new strategy to probe the structures and the biological properties of amyloid oligomers.

Controlling the Oligomerization State of Abeta-Derived Peptides with Light.,Salveson PJ, Haerianardakani S, Thuy-Boun A, Kreutzer AG, Nowick JS J Am Chem Soc. 2018 May 2;140(17):5842-5852. doi: 10.1021/jacs.8b02658. Epub 2018, Apr 20. PMID:29627987<ref>PMID:29627987</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 6cg3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Nowick, J S]]
[[Category: Salveson, P J]]
[[Category: Abeta]]
[[Category: Alzheimer's disease]]
[[Category: Amyloid]]
[[Category: Neuropeptide]]
[[Category: Oligomer]]