Journal article
An Fc Domain Protein-Small Molecule Conjugate as an Enhanced lmmunomodulator
Journal of the American Chemical Society, v 136(9), pp 3370-3373
05 Mar 2014
PMID: 24533830
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Proteins as well as small molecules have demonstrated success as therapeutic agents, but their pharmacologic properties sometimes fall short against particular drug targets. Although the adenosine 2a receptor (A(2A)R) has been identified as a promising target for immunotherapy, small molecule A(2A)R agonists have suffered from short pharmacokinetic half-lives and the potential for toxicity by modulating nonimmune pathways. To overcome these limitations, we have tethered the AR agonist CGS-21680 to the immunoglobulin Fc domain using expressed protein ligation with Sf9 cell secreted protein. The protein small molecule conjugate Fc-CGS retained potent Fc receptor and A(2A)R interactions and showed superior properties as a therapeutic for the treatment of a mouse model of autoimmune pneumonitis. This approach may provide a general strategy for optimizing small molecule therapeutics.
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Details
- Title
- An Fc Domain Protein-Small Molecule Conjugate as an Enhanced lmmunomodulator
- Creators
- Meng-Jung Chiang - Johns Hopkins MedicineMarc A. Holbert - Johns Hopkins UniversityJay H. Kalin - Johns Hopkins UniversityYoung-Hoon Ahn - Johns Hopkins UniversityJohn Giddens - University of Maryland, BaltimoreMohammed N. Amin - MED InstituteMartin S. Taylor - Johns Hopkins UniversitySamuel L. Collins - Johns Hopkins MedicineYee Chan-Li - Johns Hopkins UniversityAdam Waickman - Johns Hopkins UniversityPo-Yuan Hsiao - Johns Hopkins MedicineDavid Bolduc - Johns Hopkins UniversityDaniel J. Leahy - Johns Hopkins MedicineMaureen R. Horton - Johns Hopkins MedicineLai-Xi Wang - University of Maryland, BaltimoreJonathan D. Powell - Johns Hopkins UniversityPhilip A. Cole - Johns Hopkins University
- Publication Details
- Journal of the American Chemical Society, v 136(9), pp 3370-3373
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 4
- Grant note
- T32 AI007247 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) T32GM007309 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P01HL010342 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P01 HL010342 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 CA074305 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32AI007247 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01CA074305 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 GM096973; R01 GM099321; F32 GM108364; T32 GM007309 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Web of Science ID
- WOS:000332684700013
- Scopus ID
- 2-s2.0-84897714566
- Other Identifier
- 991020100072104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary