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Glycopeptide probes for understanding peptide specificity of the folding sensor enzyme UGGT
Affiliation:1. Discovery Chemistry, Erl Wood Manor, Lilly Research Laboratories, A Division of Eli Lilly and Company, Sunningdale Road, Windlesham, Surrey GU20 6PH, UK;2. Discovery Chemistry, Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA;3. Neuroscience Discovery, Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA;4. Musculoskeletal Research, Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA;1. College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Republic of Korea;2. New Drug Preclinical & Analytical Team, Life Science R&D Center, SK Chemicals, 310 Pangyo-ro, 463-400, Republic of Korea;3. College of Pharmacy and BK21 PLUS R-FIND Team, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang, Gyeonggi-do 410-820, Republic of Korea;4. College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea;1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;2. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA;3. Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA;4. Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA;5. Vanderbilt Institute of Chemical Biology, Vanderbilt University/Vanderbilt University Medical Center, Nashville, TN 37232, USA;1. Department of Pharmaceutical Science, Università degli Studi, Via Celoria 2, 20100 Milano, Italy;2. Department of Health Sciences, Università degli Studi, Via A. Di Rudinì 8, 20142 Milano, Italy;3. S. Paolo Hospital, Via A. Di Rudinì 8, 20142 Milano, Italy;1. Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-343, Republic of Korea;2. Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Yuseong-gu, Daejeon 305-350, Republic of Korea;1. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;2. Department of Neuroscience, Maastricht University, Maastricht, the Netherlands
Abstract:A systematic series of chitobiose-modified pentapeptides with sequence variations of hydrophobic leucine and hydrophilic serine were synthesized. The resulting glycopeptides were used as molecular probes to elucidate aglycon peptide specificity of the glycoprotein-folding sensor enzyme UGGT. Inhibitory experiments with a synthetic fluorescent glyco-substrate and the glycopeptides revealed that UGGT prefers a serine residue directly linked to C-terminal of the N-glycosylation site in its substrate recognition.
Keywords:Glycopeptide  Enzyme  Protein folding  Inhibitor  Specificity
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