High-affinity pan-specific monoclonal antibodies that target cysteinyl leukotrienes and show efficacy in an acute model of colitis.

Journal of Lipid Research
Ashlee N KingTom Huxford

Abstract

Cysteinyl leukotrienes (CysLTs) are a small family of biological signaling lipids produced by active leukocytes that contribute to diverse inflammatory disease states as a consequence of their engagement with dedicated G protein-coupled receptors. Immunization of mice with a CysLT-modified hapten carrier protein yielded novel monoclonal antibodies that display variable binding affinity to CysLTs. Solution binding assays indicated differing specificities among the antibodies tested, with antibody 10G4 displaying a preference for leukotriene C4 (LTC4). X-ray crystallography of a humanized 10G4 Fab fragment in complex with LTC4 revealed that binding induces a hook-like conformation within the hydrocarbon tail of the lipid arachidonic acid moiety. Specific hydrogen bonding to the LTC4 carboxylate groups further stabilized the complex, while a water molecule mediated a hydrogen bond network that connected the N-terminal arm of l-glutathione to both the arachidonyl carboxylate of LTC4 and the antibody heavy chain. Prophylactic administration of two anti-CysLT antibodies in mice followed by challenge with LTC4 demonstrated their in vivo efficacy against acute inflammation in a vascular permeability model. 10G4 ameliorated the effects ...Continue Reading

References

Feb 5, 1991·Biochimica Et Biophysica Acta·M ReinkeK Brune
Oct 10, 1991·Biochimica Et Biophysica Acta·C AntoineP Pradelles
Jul 16, 1985·Biochemical and Biophysical Research Communications·L OrningS Hammarström
Aug 1, 1985·Naunyn-Schmiedeberg's Archives of Pharmacology·X Y HuaP Hedqvist
Dec 4, 1980·Nature·S E DahlénB Samuelsson
Oct 31, 1980·Biochemical and Biophysical Research Communications·O RådmarkB Samuelsson
Jul 1, 1980·Allergy·B SamuelssonP Borgeat
May 1, 1995·Journal of Pediatric Gastroenterology and Nutrition·J H KimP M Sherman
Mar 1, 1995·American Journal of Respiratory and Critical Care Medicine·D DavidsonB A Wilkens
Dec 1, 1993·Annals of Internal Medicine·E IsraelJ M Drazen
Jun 14, 2000·The Journal of Biological Chemistry·C E HeiseJ F Evans
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
May 12, 2005·Journal of Molecular Biology·Edwin PozharskiDagmar Ringe
Jun 8, 2006·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Zhong HuaXiang Mingming
Feb 21, 2008·Inflammatory Bowel Diseases·Françoise Stanke-LabesqueBruno Bonaz
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan M WojciakTom Huxford
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Aug 10, 2010·Acta Crystallographica. Section D, Biological Crystallography·Galina ObmolovaGary L Gilliland
Sep 8, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yan ZhouShenghua Jie
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Mar 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Michiko K OyoshiRaif S Geha
May 15, 2013·Nucleic Acids Research·Jian YeJames M Ostell
Feb 11, 2014·Current Protocols in Immunology·Benoit ChassaingMatam Vijay-Kumar
Jul 6, 2014·Allergy, Asthma & Immunology Research·Yoshihide Kanaoka, Joshua A Boyce
May 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Lora G BankovaNora A Barrett
Sep 22, 2016·Journal of Biochemistry·Yuki KawakamiYoshitaka Takahashi
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Apr 23, 2020·Antibodies·Elinaz FarokhiTom Huxford

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