Shaofei Ji

Stability testing and metabolite profiling to support optimization of cyclic peptides for oral delivery

Ramaswamy A. Iyer, Shaofei Ji, Jianyao Wang, Saro Mardirosian et autres

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Simultaneous quantification of siRNA antisense and sense strands by hybrid liquid chromatography-mass spectrometry

Karan Agrawal, Shaofei Ji, Wenying Jian

BACKGROUND: Most oligonucleotide bioanalytical assays currently only quantify the pharmacologically-active antisense strand, though there have been recent efforts to simultaneously quantify the sense strand using hybridization ELISA or solid phase extraction LC-MS. Hybrid LC-MS, which offers both high sensitivity and specificity unlike …

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Comparison of multiple bioanalytical assay platforms for the quantitation of siRNA therapeutics

Karan Agrawal, Laurelle K Calliste, Shaofei Ji, Shengsheng Xu et autres

Aim: Oligonucleotide therapeutics can be quantified using various bioanalytical methods, and these methods have been compared extensively. However, few comparisons exist where the same analyte is evaluated by multiple assay platforms.Materials & methods: Hybrid LC-MS, SPE-LC-MS, HELISA and SL-RT-qPCR methods were developed …

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Discovery of a Novel, First-in-Class Bfl-1 BH3 Mimetic with Pro-Apoptotic Activity

Maarten Derks, Marian C. Bryan, Cindy Rockx, Tamara Schults et autres

Background: Intrinsic apoptosis is regulated by the B Cell lymphoma 2 (BCL-2) protein family. Anti-apoptotic family members, such as BCL-2, MCL-1 and BFL-1, sequester their pro-apoptotic counterparts through a highly conserved BH3 binding groove. Disruption of this balance leads to mitochondrial pore …

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Ubiquitin signaling and the proteasome drive human DNA–protein crosslink repair

Maram M. Essawy, Lisa N. Chesner, Duha Alshareef, Shaofei Ji et autres

DNA-protein crosslinks (DPCs) are large cytotoxic DNA lesions that form following exposure to chemotherapeutic drugs and environmental chemicals. Nucleotide excision repair (NER) and homologous recombination (HR) promote survival following exposure to DPC-inducing agents. However, it is not known how cells recognize DPC …

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Evaluating the Use of Locked Nucleic Acid Capture Probes in Hybrid LC–MS/MS Analysis of siRNA Analytes

Karan Agrawal, Lijuan Kang, Shaofei Ji, Jennyfer Tena et autres

Background: Hybrid LC–MS assays for oligonucleotides rely on capture probes to develop assays with high sensitivity and specificity. Locked nucleic acid (LNA) probes are thermodynamically superior to existing capture probes, but are not currently used for hybrid LC–MS assays. Materials & methods: …

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An Integrated Strategy for Assessing the Metabolic Stability and Biotransformation of Macrocyclic Peptides in Drug Discovery toward Oral Delivery

Yukuang Guo, Shaofei Ji, Wei Wang, Susan Wong et autres

Macrocyclic peptides (MCPs) are an emerging class of promising drug modalities that can be used to interrogate hard-to-drug (“undruggable”) targets. However, their poor intestinal stability is one of the major liabilities or obstacles for oral drug delivery. We therefore investigated the metabolic …

5-Formylcytosine-induced DNA–peptide cross-links reduce transcription efficiency, but do not cause transcription errors in human cells

Shaofei Ji, Daeyoon Park, Konstantin Y. Kropachev, Marina Kolbanovskiy et autres

5-Formylcytosine (5fC) is an endogenous epigenetic DNA mark introduced via enzymatic oxidation of 5-methyl-dC in DNA. We and others recently reported that 5fC can form reversible DNA–protein conjugates with histone proteins, likely contributing to regulation of nucleosomal organization and gene expression. The …

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Transcriptional Bypass of DNA–Protein and DNA–Peptide Conjugates by T7 RNA Polymerase

Shaofei Ji, Jenna Thomforde, Colette B. Rogers, Iwen Fu et autres

DNA–protein cross-links (DPCs) are unusually bulky DNA adducts that block the access of proteins to DNA and interfere with gene expression, replication, and repair. We previously described DPC formation at the N7-guanine position of DNA in human cells treated with antitumor nitrogen …

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Error-prone replication of a 5-formylcytosine-mediated DNA-peptide cross-link in human cells

Spandana Naldiga, Shaofei Ji, Jenna Thomforde, Claudia M. Nicolae et autres

DNA-protein cross-links can interfere with chromatin architecture, block DNA replication and transcription, and interfere with DNA repair. Here we synthesized a DNA 23-mer containing a site-specific DNA-peptide cross-link (DpC) by cross-linking an 11-mer peptide to the DNA epigenetic mark 5-formylcytosine in synthetic …

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Chemistry and Biology of DNA-protein cross-links

Shaofei Ji

University of Minnesota Ph.D. dissertation. February 2019. Major: Chemistry. Advisor: Natalia Tretyakova. 1 computer file (PDF); xxxvii, 373 pages.

5-Formylcytosine mediated DNA–protein cross-links block DNA replication and induce mutations in human cells

Shaofei Ji, Iwen Fu, Spandana Naldiga, Hongzhao Shao et autres

Nucleic Acids Research, 46(13):6455–6469, https://doi.org/10.1093/nar/gky444 There was a typographical error on page 6458, column 1, line 12 and on page 6459, column 2, line 53. In both instances, dNTP concentrations should be listed as ‘5, 10, 25, 50, 100, 150, 250, 500 …

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