View source for 5ojt


==Structure-Activity Relationships and Biological Characterization of a Novel, Potent and Serum Stable C-X-C chemokine receptor type 4 (CXCR4) Antagonist==
<StructureSection load='5ojt' size='340' side='right'caption='[[5ojt]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ojt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OJT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=LE1:3-SULFANYL-L-VALINE'>LE1</scene>, <scene name='pdbligand=NAL:BETA-(2-NAPHTHYL)-ALANINE'>NAL</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=5ojt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ojt OCA], [https://pdbe.org/5ojt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ojt RCSB], [https://www.ebi.ac.uk/pdbsum/5ojt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ojt ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In our ongoing pursuit of CXCR4 antagonists as potential anticancer agents, we recently developed a potent, selective, and plasma stable peptide, Ac-Arg-Ala-[d-Cys-Arg-Phe-Phe-Cys]-COOH (3). Nevertheless, this compound was still not potent enough (IC50 approximately 53 nM) to enter preclinical studies. Thus, a lead-optimization campaign was here undertaken to further improve the binding affinity of 3 while preserving its selectivity and proteolytic stability. Specifically, extensive structure-activity relationships (SARs) investigations were carried out on both its aromatic and disulfide forming amino acids. One among the synthesized analogue, Ac-Arg-Ala-[d-Cys-Arg-Phe-His-Pen]-COOH (19), displayed subnanomolar affinity toward CXCR4, with a marked selectivity over CXCR3 and CXCR7. NMR and molecular modeling studies disclosed the molecular bases for the binding of 19 to CXCR4 and for its improved potency compared to the lead 3. Finally, biological assays on specific cancer cell lines showed that 19 can impair CXCL12-mediated cell migration and CXCR4 internalization more efficiently than the clinically approved CXCR4 antagonist plerixafor.

Structure-Activity Relationships and Biological Characterization of a Novel, Potent, and Serum Stable C-X-C Chemokine Receptor Type 4 (CXCR4) Antagonist.,Di Maro S, Di Leva FS, Trotta AM, Brancaccio D, Portella L, Aurilio M, Tomassi S, Messere A, Sementa D, Lastoria S, Carotenuto A, Novellino E, Scala S, Marinelli L J Med Chem. 2017 Nov 20. doi: 10.1021/acs.jmedchem.7b01062. PMID:29125295<ref>PMID:29125295</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ojt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brancaccio D]]
[[Category: Carotenuto A]]