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Cardio Program of Excellence in Glycosciences

Upcoming Seminars

Cardio PEG Lab Meetings

(Physiology 612, 9.30-11)

This meeting is suspended over the summer. Watch this space for updates.


Cardio PEG Retreat

(Mt Washington Conference Center)

July 15th, Register by July 5th @ CardioPEG Registration

Schedule: Final Rev PEG 2016 Retreat Sched[1].pdfFinal Rev PEG 2016 Retreat Sched[1].pdf


Glycobiology Interest Group

This meeting is suspended over the summer. Watch this space for updates.

Upcoming Classwork

January 2017: Fundamentals of Glycobiology

July 2017: Techniques in Glycobiology


C3: The Chemistry Core

Synopsis: Analysis of glycoconjugate structure and understanding the function of these complex molecules can often be facilitated by chemical approaches and compounds that are not commercially available. To help meet this need, the Chemistry Core, which is headed Kevin Yarema who is a leader in chemical glycobiology, is well equipped for the routine synthesis of many bioorganic small molecules required to manipulate glycosylation. The core specializes in monosaccharide analogues used in “metabolic glycoengeering” technology; it is pursuing inhibitors of the hexosamine biosynthetic pathway (specifically UAP1/2) and glycosyltransferases; and it is developing methods to improve the pharmacological properties of sugar based drugs to facilitate their in vivo use and clinical translation. The core also provides expertise is other aspects as chemical synthesis, including the production of PEG-SA-based polymers for in vivo delivery of D-PDMP used in Project 5 (see accompanying reference list). The Chemistry Core provides support to other CardioPEG projects and participated in its training mission to provide “hands-on” experience as well as theoretical knowledge in cutting-edge chemical glycobiology.

Resources  Now Available: The chemistry core primarily provides monosaccharide analogues for metabolic glycan labeling on a collaborative basis that are not commercially available. Such compounds that are currently available include 1,3,4-O-Bu3ManNAc, 3,4,6-O-Bu3ManNAc, Bu4ManNAc, 1,3,4-O-Bu3ManNAz, 3,4,6-O-Bu3ManNAz, and Bu4ManNAz, which are tools that benefit metabolic labeling experiments underway in Projects 1 through 4.  In addition, a newly-developed resource is Ac4Glc2Bz, a novel inhibitor of UAP1/2 that reduces flux through the hexosamine biosynthetic pathway, lowers levels of UDP-GlcNAc, and reduces O-GlcNAcylation by depriving OGT of this critical co-substrate; this new tool is relevant to the research ongoing in Projects 1 and 2. Additional compounds can be custom synthesized upon request; alternately advice on their synthesis and characterization can be provided.

Requests should be made to:


Kevin J. Yarema Ph.D.
Associate Professor of Biomedical Engineering

Smith Building, 5029
The Translation Tissue Engineering Center
400 North Broadway
Baltimore, MD 21231

Phone: 410.614.6835
Fax: 410.614.6840
Email: kyarema1@jhu.edu
website: YaremaLab


Selected References (“*” indicates collaborative CardioPEG projects)

“High-flux” butanoylated hexosamine analogs for metabolic labeling:

Wang, Z., Du, J., Che, P.-L., Meledeo, M.A. & Yarema, K.J. Hexosamine analogs: from metabolic glycoengineering to drug discovery. Current Opinion in Chemical Biology 13, 565-572 (2009).

Almaraz, R.T., Aich, U., Khanna, H.S., Tan, E., Bhattacharya, R., Shah, S. & Yarema, K.J. Metabolic oligosaccharide engineering with N-acyl functionalized ManNAc analogues: cytotoxicity, metabolic flux, and glycan-display considerations. Biotechnology and Bioengineering 109, 992-1006 (2012).

* Almaraz, R.T., Tian, Y., Bhattarcharya, R., Tan, E., Chen, S.-H., Dallas, M.R., Chen, L., Zhang, Z., Zhang, H., Konstantopoulos, K. & Yarema, K.J. Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis. Molecular & Cellular Proteomics, 10.1074/mcp.M1112.017558 (2012).

* Shah, P., Yang, S., Sun, S., Aiyetan, P., Yarema, K.J. & Zhang, H. Mass spectrometric analysis of sialylated glycans using solid phase labeling of sialic acids. Analytical Chemistry 85, 3606-3613 (2013).

* Tian, Y., Almaraz, R.T., Chio, C., Li, Q.K., Saeui, C., LI, D., Shad, P., Bhattacharya, R., Yarema, K.J. & Zhang, H. Identification of sialylated glycoproteins from metabolically oligosaccharide engineered pancreatic cells. Clinical Proteomics 12, Article 11 ( doi: 10.1186/s12014-12015-19083-12018. eCollection 12015) (2015).


In vivo delivery of small molecules (e.g., butanoylated sugars and D-PDMP used in Project 5):

Aich, U., Meledeo, M.A., Sampathkumar, S.-G., Fu, J., Jones, M.B., Weier, C.A., Chung, S.Y., Tang, B.C., Yang, M., Hanes, J. & Yarema, K.J. Development of delivery methods for carbohydrate-based drugs: controlled release of biologically-active short chain fatty acid-hexosamine analogs. Glycoconjugate Journal 27, 445-459 (2010).

* Mishra, S., Bedja, D., Amuzie, C., Foss, C.A., Pomper, M.G., Bhattacharya, R., Yarema, K.J. & Chatterjee, S. Improved intervention of atherosclerosis and cardiac hypertrophy through biodegradable polymer-encapsulated delivery of glycosphingolipid inhibitor. Biomaterials 64, 125-135 (2015).

Kim, C., Shores, L., Guo, Q., Aly, A., Jeon, O.H., Kim , d.H., Bernstein, N., Bhattacharya, R., Chae, J.J., Yarema, K.J. & Elisseeff, J.H. Electrospun microfiber scaffolds with anti-Inflammatory tributanoylated N-acetyl-d-glucosamine promote cartilage regeneration. Tissue Engineering, Part A 22, 689-697 (2016).

 

Kim, C., Jeon, O.H., Kim, d.H., Chae, J.J., Shores, L., Bernstein, N., Bhattacharya, R., Coburn, J.M., Yarema, K.J. & Elisseeff, J.H. Local delivery of a carbohydrate analog for reducing arthritic inflammation and rebuilding cartilage. Biomaterials 83, 93-101 (2016).


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