Identification of a PCSK9-LDLR disruptor peptide with in vivo function

Brousseau, Margaret E.; Clairmont, Kevin B.; Spraggon, Glen; Flyer, Alec N.; Golosov, Andrei A.; Grosche, Philipp; Amin, Jakal; Andre, Jerome; Burdick, Debra; Caplan, Shari; Chen, Guanjing; Chopra, Raj; Ames, Lisa; Dubiel, Diana; Fan, Li; Gattlen, Raphael; Kelly-Sullivan, Dawn; Koch, Alexander W.; Lewis, Ian; Li, Jingzhou; Liu, Eugene; Lubicka, Danuta; Marzinzik, Andreas; Nakajima, Katsumasa; Nettleton, David; Ottl, Johannes; Pan, Meihui; Patel, Tajesh; Perry, Lauren; Pickett, Stephanie; Poirier, Jennifer; Reid, Patrick C.; Pelle, Xavier; Seepersaud, Mohindra; Subramanian, Vanitha; Vera, Victoria; Xu, Mei; Yang, Lihua; Yang, Qing; Yu, Jinghua; Zhu, Guoming; Monovich, Lauren G.

doi:10.1016/j.chembiol.2021.08.012

Identification of a PCSK9-LDLR disruptor peptide with in vivo function

Journal Article · 01 February 2022 · Cell Chem. Biol.

DOI:https://doi.org/10.1016/j.chembiol.2021.08.012· OSTI ID:1847145

Brousseau, Margaret E.; Clairmont, Kevin B.; Spraggon, Glen; Flyer, Alec N.; Golosov, Andrei A.; Grosche, Philipp; Amin, Jakal; Andre, Jerome; Burdick, Debra; Caplan, Shari; Chen, Guanjing; Chopra, Raj; Ames, Lisa; Dubiel, Diana; Fan, Li; Gattlen, Raphael; Kelly-Sullivan, Dawn; Koch, Alexander W.; Lewis, Ian; Li, Jingzhou more »

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: DOE - Office Of Science; INDUSTRY

OSTI ID:: 1847145

Journal Information:: Cell Chem. Biol., Vol. 29, Issue (2)

Country of Publication:: United States

Language:: ENGLISH

References (44)

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia Abifadel, Marianne; Varret, Mathilde; Rabès, Jean-Pierre Nature Genetics, Vol. 34, Issue 2 https://doi.org/10.1038/ng1161	journal	May 2003
LDL-R promoting activity of peptides derived from human PCSK9 catalytic domain (153–421): Design, synthesis and biochemical evaluation Alghamdi, Rasha H.; O'Reilly, Paul; Lu, Chunyu European Journal of Medicinal Chemistry, Vol. 92 https://doi.org/10.1016/j.ejmech.2015.01.022	journal	March 2015
Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design Alleyne, Candice; Amin, Rupesh P.; Bhatt, Bhavana Journal of Medicinal Chemistry, Vol. 63, Issue 22 https://doi.org/10.1021/acs.jmedchem.0c01084	journal	November 2020
A receptor-mediated pathway for cholesterol homeostasis Brown, Ms; Goldstein, Jl Science, Vol. 232, Issue 4746 https://doi.org/10.1126/science.3513311	journal	April 1986
Design of Organo-Peptides As Bipartite PCSK9 Antagonists Burdick, Daniel J.; Skelton, Nicholas J.; Ultsch, Mark ACS Chemical Biology, Vol. 15, Issue 2 https://doi.org/10.1021/acschembio.9b00899	journal	January 2020
Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia Cunningham, David; Danley, Dennis E.; Geoghegan, Kieran F. Nature Structural & Molecular Biology, Vol. 14, Issue 5 https://doi.org/10.1038/nsmb1235	journal	April 2007
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove Evison, Benny J.; Palmer, James T.; Lambert, Gilles Bioorganic & Medicinal Chemistry, Vol. 28, Issue 6 https://doi.org/10.1016/j.bmc.2020.115344	journal	March 2020
Design of Thioether Cyclic Peptide Scaffolds with Passive Permeability and Oral Exposure Golosov, Andrei A.; Flyer, Alec N.; Amin, Jakal Journal of Medicinal Chemistry, Vol. 64, Issue 5 https://doi.org/10.1021/acs.jmedchem.0c01505	journal	February 2021
Flexizymes for genetic code reprogramming Goto, Yuki; Katoh, Takayuki; Suga, Hiroaki Nature Protocols, Vol. 6, Issue 6 https://doi.org/10.1038/nprot.2011.331	journal	May 2011
Fragment-based design of small molecule PCSK9 inhibitors using simulated annealing of chemical potential simulations Guarnieri, Frank; Kulp, John L.; Kulp, John L. PLOS ONE, Vol. 14, Issue 12 https://doi.org/10.1371/journal.pone.0225780	journal	December 2019
The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain Hampton, E. N.; Knuth, M. W.; Li, J. Proceedings of the National Academy of Sciences, Vol. 104, Issue 37 https://doi.org/10.1073/pnas.0703402104	journal	September 2007
The 1.8 A crystal structure of a proteinase K-like enzyme from a psychrotroph Serratia species Helland, Ronny; Larsen, Atle Noralf; Smalas, Arne Oskar FEBS Journal, Vol. 273, Issue 1 https://doi.org/10.1111/j.1742-4658.2005.05040.x	journal	January 2006
TRAP Display: A High-Speed Selection Method for the Generation of Functional Polypeptides Ishizawa, Takahiro; Kawakami, Takashi; Reid, Patrick C. Journal of the American Chemical Society, Vol. 135, Issue 14 https://doi.org/10.1021/ja312579u	journal	March 2013
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Molecular basis for LDL receptor recognition by PCSK9 Kwon, H. J.; Lagace, T. A.; McNutt, M. C. Proceedings of the National Academy of Sciences, Vol. 105, Issue 6 https://doi.org/10.1073/pnas.0712064105	journal	February 2008
Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix Liebschner, Dorothee; Afonine, Pavel V.; Baker, Matthew L. Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 10 https://doi.org/10.1107/S2059798319011471	journal	October 2019
Small Molecule Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Hit to Lead Optimization of Systemic Agents Londregan, Allyn T.; Wei, Liuqing; Xiao, Jun Journal of Medicinal Chemistry, Vol. 61, Issue 13 https://doi.org/10.1021/acs.jmedchem.8b00650	journal	January 2018
Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH Surdo, Paola Lo; Bottomley, Matthew J.; Calzetta, Alessandra EMBO reports, Vol. 12, Issue 12 https://doi.org/10.1038/embor.2011.205	journal	November 2011
Annexin A2 Reduces PCSK9 Protein Levels via a Translational Mechanism and Interacts with the M1 and M2 Domains of PCSK9 Ly, Kévin; Luna Saavedra, Yascara Grisel; Canuel, Maryssa Journal of Biological Chemistry, Vol. 289, Issue 25 https://doi.org/10.1074/jbc.M113.541094	journal	June 2014
Annexin A2 Is a C-terminal PCSK9-binding Protein That Regulates Endogenous Low Density Lipoprotein Receptor Levels Mayer, Gaétan; Poirier, Steve; Seidah, Nabil G. Journal of Biological Chemistry, Vol. 283, Issue 46 https://doi.org/10.1074/jbc.M805971200	journal	November 2008
Liver-Targeted Small-Molecule Inhibitors of Proprotein Convertase Subtilisin/Kexin Type 9 Synthesis McClure, Kim F.; Piotrowski, David W.; Petersen, Donna Angewandte Chemie International Edition, Vol. 56, Issue 51 https://doi.org/10.1002/anie.201708744	journal	November 2017
Pharmacologic Profile of the Adnectin BMS-962476, a Small Protein Biologic Alternative to PCSK9 Antibodies for Low-Density Lipoprotein Lowering Mitchell, Tracy; Chao, Ginger; Sitkoff, Doree Journal of Pharmacology and Experimental Therapeutics, Vol. 350, Issue 2 https://doi.org/10.1124/jpet.114.214221	journal	June 2014
A Small-Molecule Anti-secretagogue of PCSK9 Targets the 80S Ribosome to Inhibit PCSK9 Protein Translation Petersen, Donna N.; Hawkins, Julie; Ruangsiriluk, Wanida Cell Chemical Biology, Vol. 23, Issue 11 https://doi.org/10.1016/j.chembiol.2016.08.016	journal	November 2016
From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9 Petrilli, Whitney L.; Adam, Gregory C.; Erdmann, Roman S. Cell Chemical Biology, Vol. 27, Issue 1 https://doi.org/10.1016/j.chembiol.2019.10.002	journal	January 2020
The Crystal Structure of PCSK9: A Regulator of Plasma LDL-Cholesterol Piper, Derek E.; Jackson, Simon; Liu, Qiang Structure, Vol. 15, Issue 5 https://doi.org/10.1016/j.str.2007.04.004	journal	May 2007
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol Ray, Kausik K.; Wright, R. Scott; Kallend, David New England Journal of Medicine, Vol. 382, Issue 16 https://doi.org/10.1056/NEJMoa1912387	journal	April 2020
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease Sabatine, Marc S.; Giugliano, Robert P.; Keech, Anthony C. New England Journal of Medicine, Vol. 376, Issue 18 https://doi.org/10.1056/NEJMoa1615664	journal	May 2017
Design and Synthesis of Truncated EGF-A Peptides that Restore LDL-R Recycling in the Presence of PCSK9 In Vitro Schroeder, Christina I.; Swedberg, Joakim E.; Withka, Jane M. Chemistry & Biology, Vol. 21, Issue 2 https://doi.org/10.1016/j.chembiol.2013.11.014	journal	February 2014
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome Schwartz, Gregory G.; Steg, P. Gabriel; Szarek, Michael New England Journal of Medicine, Vol. 379, Issue 22 https://doi.org/10.1056/NEJMoa1801174	journal	November 2018
Annexin A2 Is a Natural Extrahepatic Inhibitor of the PCSK9-Induced LDL Receptor Degradation Seidah, Nabil G.; Poirier, Steve; Denis, Maxime PLoS ONE, Vol. 7, Issue 7 https://doi.org/10.1371/journal.pone.0041865	journal	July 2012
PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide Shan, LiXin; Pang, Ling; Zhang, Rumin Biochemical and Biophysical Research Communications, Vol. 375, Issue 1 https://doi.org/10.1016/j.bbrc.2008.07.106	journal	October 2008
Disrupting the PCSK9/LDLR protein–protein interaction by an imidazole-based minimalist peptidomimetic Stucchi, Mattia; Grazioso, Giovanni; Lammi, Carmen Organic & Biomolecular Chemistry, Vol. 14, Issue 41 https://doi.org/10.1039/C6OB01642A	journal	January 2016
Small Molecule Inhibitors of the PCSK9·LDLR Interaction Taechalertpaisarn, Jaru; Zhao, Bosheng; Liang, Xiaowen Journal of the American Chemical Society, Vol. 140, Issue 9 https://doi.org/10.1021/jacs.7b09360	journal	January 2018
Engineered EGF-A Peptides with Improved Affinity for Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Tombling, Benjamin J.; Lammi, Carmen; Lawrence, Nicole ACS Chemical Biology, Vol. 16, Issue 2 https://doi.org/10.1021/acschembio.0c00991	journal	January 2021
Bioactive Cyclization Optimizes the Affinity of a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Peptide Inhibitor Tombling, Benjamin J.; Lammi, Carmen; Lawrence, Nicole Journal of Medicinal Chemistry, Vol. 64, Issue 5 https://doi.org/10.1021/acs.jmedchem.0c01766	journal	December 2020
Time-Averaged Distributions of Solute and Solvent Motions: Exploring Proton Wires of GFP and PfM2DH Velez-Vega, Camilo; McKay, Daniel J. J.; Aravamuthan, Vibhas Journal of Chemical Information and Modeling, Vol. 54, Issue 12 https://doi.org/10.1021/ci500571h	journal	November 2014
How proteins bind macrocycles Villar, Elizabeth A.; Beglov, Dmitri; Chennamadhavuni, Spandan Nature Chemical Biology, Vol. 10, Issue 9 https://doi.org/10.1038/nchembio.1584	journal	July 2014
Data processing and analysis with the autoPROC toolbox Vonrhein, Clemens; Flensburg, Claus; Keller, Peter Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911007773	journal	March 2011
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation Weider, Elodie; Susan-Resiga, Delia; Essalmani, Rachid Journal of Biological Chemistry, Vol. 291, Issue 32 https://doi.org/10.1074/jbc.M116.717736	journal	August 2016
Binding of Proprotein Convertase Subtilisin/Kexin Type 9 to Epidermal Growth Factor-like Repeat A of Low Density Lipoprotein Receptor Decreases Receptor Recycling and Increases Degradation Zhang, Da-Wei; Lagace, Thomas A.; Garuti, Rita Journal of Biological Chemistry, Vol. 282, Issue 25 https://doi.org/10.1074/jbc.M702027200	journal	April 2007
Calcium-Independent Inhibition of PCSK9 by Affinity-Improved Variants of the LDL Receptor EGF(A) Domain Zhang, Yingnan; Zhou, Lijuan; Kong-Beltran, Monica Journal of Molecular Biology, Vol. 422, Issue 5 https://doi.org/10.1016/j.jmb.2012.06.018	journal	October 2012
Identification of a Small Peptide That Inhibits PCSK9 Protein Binding to the Low Density Lipoprotein Receptor Zhang, Yingnan; Eigenbrot, Charles; Zhou, Lijuan Journal of Biological Chemistry, Vol. 289, Issue 2 https://doi.org/10.1074/jbc.M113.514067	journal	November 2013
Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists Zhang, Yingnan; Ultsch, Mark; Skelton, Nicholas J. Nature Structural & Molecular Biology, Vol. 24, Issue 10 https://doi.org/10.1038/nsmb.3453	journal	August 2017

Similar Records

Hyperhomocysteinemia and hyperandrogenemia share PCSK9-LDLR pathway to disrupt lipid homeostasis in PCOS

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23105693

Mondal, Kalyani; Chakraborty, Pratip

In Silico Insights into Protein–Protein Interaction Disruptive Mutations in the PCSK9-LDLR Complex

Journal Article · 2020 · International Journal of Molecular Sciences (Online) · OSTI ID:1877977

Martin, William R.; Lightstone, Felice C.; Cheng, Feixiong

In Silico Insights into Protein–Protein Interaction Disruptive Mutations in the PCSK9-LDLR Complex

Journal Article · 2020 · International Journal of Molecular Sciences (Online) · OSTI ID:1628389

Martin, William R.; Lightstone, Felice C.; Cheng, Feixiong

Identification of a PCSK9-LDLR disruptor peptide with in vivo function

Citation Formats

References (44)

Similar Records

Related Subjects