Review
Biochemical Research Methods
Yiao Wang, Carston R. Wagner, Mark D. Distefano
Summary: The homeostasis of cellular activities is crucial for the normal functioning of organisms. Protein conjugates, as hybrid biomacromolecules, have shown great potential in manipulating cell function for therapeutic applications such as cancer treatment, tissue engineering, and regenerative medicine. This review discusses recent progress in the design and assembly of protein conjugates, including different categories based on their mechanisms of action, conjugation methodologies, and potential biomedical applications.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ding Wei, Yurong Mao, Zili Xu, Jiakang Chen, Jiusheng Li, Biao Jiang, Hongli Chen
Summary: This study synthesized three rationally designed triptolide drug-linkers for the specific construction of ADCs, which displayed high anti-tumor potency against HER2-targeted cancer. The incorporation of stable carbamates and hydrophilic PEG chains improved the stability and hydrophilicity of the drug-linkers.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Xing Huang, Meng Chen, Zhan Huang, Yanfei Zhang, Taorong Shen, Yakun Shi, Yanli Tong, Xiaoyong Zou, Si-Yang Liu, Jianhe Guo, Zong Dai
Summary: In this study, a novel DNA nanodevice was proposed for dual-biomarker sensing, enabling highly specific imaging of cancer cells. By performing transmembrane logic operations from the cell membrane to the cytoplasm, the nanodevice achieved reliable analysis of intracellular biomarkers such as nucleolin protein and microRNAs.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Zhefu Dai, Xiao-Nan Zhang, Qinqin Cheng, Fan Fei, Tianling Hou, Jiawei Li, Alireza Abdolvahabi, Junji Watanabe, Hua Pei, Goar Smbatyan, Jianming Xie, Heinz-Josef Lenz, Stan G. Louie, Yong Zhang
Summary: A new technology for producing homogeneous ADCs, ARC-ADCs, was developed by utilizing the human CD38 catalytic domain and its derived inhibitor. Through this technology, ADCs with customizable drug-to-antibody ratios (DARs) can be rapidly generated, showing potent activity in killing hCLL-1-positive AML cells. This work provides novel ADC candidates for combating AML and supports ARC-ADC as a versatile approach for producing site-specific ADCs with defined DARs.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Analytical
Aarti Jashnani, Srikanth Kotapati, Madhura Deshpande, Sayumi Yamazoe, Pavel Strop, Arvind Rajpal, Gavin Dollinger
Summary: The traditional method of evaluating ADC biotransformation involves affinity capture on streptavidin magnetic beads followed by enzyme digestion to remove Fc and N-glycan, however, this is time-consuming and not suitable for labile ADCs. A faster method was developed where ADCs are captured on streptavidin cartridges coated with a biotinylated generic capture reagent, followed by a 15-minute enzyme digestion, and then analyzed by LC-HRMS. This method reduces sample preparation time and is applicable for any human mAb/ADC regardless of isotype.
ANALYTICAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Julien Dugal-Tessier, Srinath Thirumalairajan, Nareshkumar Jain
Summary: This article summarizes the key technological advancements in the preparation of antibody-oligonucleotide conjugates (AOCs) and discusses the distinct advantages and disadvantages of AOCs as novel therapeutics. It evaluates the merits and demerits of different methods of conjugating oligonucleotides to antibodies, mainly focusing on AOC purification and analytical characterizations. Lessons learned from in vitro and in vivo studies, particularly findings related to silencing, trafficking, and cytotoxicity of the conjugates, are also summarized.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Keyuan Xu, Jiani Han, Liu Yang, Li Cao, Shuang Li, Zhangyong Hong
Summary: Traditional antibody-drug conjugates are limited by the large molecular weight of the antibody molecules, resulting in low permeability into solid tumors. A new cleavable ADC design with improved tumor tissue permeability and a long circulation half-life was proposed by fusing the small ADC with the Fc domain of the antibody for extended circulation and inserting a digestion sequence between them. The experimental results showed significantly enhanced tumor treatment ability of the designed molecule compared to conventional ADCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yuto Honda, Sayaka Onodera, Hiroyasu Takemoto, Noor Faizah Che Harun, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Yudi Sun, Yutaka Miura, Nobuhiro Nishiyama
Summary: This study aims to develop a technology to control the activity of small interfering RNA (siRNA) in a thermo-responsive manner, even at temperatures close to body temperature. By conjugating siRNA with a thermally responsive copolymer, the activity of siRNA can be enhanced based on temperature changes. This technique offers a promising approach to selectively induce therapeutic effects of siRNA in vivo.
PHARMACEUTICAL RESEARCH
(2023)
Article
Biochemical Research Methods
Mareile Boschanski, Tobias Krueger, Lennard Karsten, Georg Falck, Sarfaraz Alam, Marcus Gerlach, Benjamin Mueller, Kristian M. Mueller, Norbert Sewald, Thomas Dierks
Summary: This study demonstrates an improved and facile strategy for functionalizing DARPin and scFv425-Fc antibodies targeting EGFR, by conjugating them with MMAE and CF for successful testing in cell culture for receptor binding, internalization, and cytotoxicity.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jisoo Park, Sangwoo Lee, Yuseon Kim, Tae Hyeon Yoo
Summary: Antibody-protein conjugates are valuable tools for studying biological systems and advancing therapeutics and diagnostics. Challenges in generating bispecific antibodies and antibody-enzyme conjugates can be addressed through enzymatic and chemical approaches, offering solutions for site-specific conjugation of antibodies with other proteins.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Barbora Malecova, Rob S. Burke, Michael Cochran, Michael D. Hood, Rachel Johns, Philip R. Kovach, Venkata R. Doppalapudi, Gulin Erdogan, J. Danny Arias, Beatrice Darimont, Christopher D. Miller, Hanhua Huang, Andrew Geall, Husam S. Younis, Arthur A. Levin
Summary: In this study, antibody-oligonucleotide conjugates (AOCs) targeting TfR1 were developed and used to deliver oligonucleotides to muscle tissue in mice and monkeys. AOCs achieved higher concentration of oligonucleotides in skeletal muscle than unconjugated siRNA. The AOCs showed significant mRNA reduction in skeletal and cardiac muscle, with minimal activity in other major organs. The results suggest the potential of AOCs as a new class of oligonucleotide therapeutics.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Qun Zhou
Summary: As antibody-drug conjugates have become crucial for cancer therapy, various approaches have been developed to achieve selective and homogeneous molecules. These methods involve engineering antibodies to introduce specific amino acids or peptides for coupling. In addition to cytotoxic compounds, these techniques can also be applied to conjugate non-cytotoxic compounds, proteins/peptides, glycans, lipids, and nucleic acids. The resulting site-specific antibody conjugates offer potential for proof-of-concept studies and the development of novel therapeutic options.
Review
Pharmacology & Pharmacy
Lei Zhang, Yayu Liang, Guohui Liang, Zhili Tian, Yue Zhang, Zhihui Liu, Xinying Ji
Summary: This article introduces RNA interference technology and its application in genetic therapy, focusing on the advantages and limitations of GalNAc-siRNA conjugates and lipid nanoparticles as delivery systems, and looking forward to the development of oligonucleotide drugs in genetic therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sooin Kim, Sanggil Kim, Sangji Kim, Namkyoung Kim, Sang Won Lee, Hanbin Yi, Seungeun Lee, Taebo Sim, Yongseok Kwon, Hyun Soo Lee
Summary: A novel method for traceless affinity-directed intact protein labeling is established using small binding proteins and genetic code expansion technology. This approach enables site-specific antibody labeling and the production of highly effective antibody-drug conjugates specifically targeting breast cancer cell lines.
Article
Polymer Science
Yi-Yang Peng, Haimei Hu, Diana Diaz-Dussan, Jianyang Zhao, Xiaojuan Hao, Ravin Narain
Summary: This study developed a novel modification strategy by conjugating cell-penetrating peptides to polymers, resulting in the formation of polymer complexes with multivalent cell-penetrating peptides. These complexes showed enhanced cellular uptake of siRNA and improved silencing efficiency through enhanced endosomal escape.
Article
Chemistry, Multidisciplinary
Zhilei Ge, Linjie Guo, Guangqi Wu, Jiang Li, Yunlong Sun, Yingqin Hou, Jiye Shi, Shiping Song, Lihua Wang, Chunhai Fan, Hua Lu, Qian Li
Article
Biochemistry & Molecular Biology
Zuowen Shi, Xu Zhang, Xiaodan Wang, Fangping Yang, Zikun Yu, Ying Ling, Hua Lu, Shifang Luan, Haoyu Tang
Article
Biochemistry & Molecular Biology
Qingxin Yao, Guangqi Wu, Hao Hao, Hua Lu, Yuan Gao
Summary: This study demonstrates a redox-triggered reversible supramolecular self-assembly process governed by the balance of two secondary conformations, where the oxidation state of the selenopolypeptide affects the conformation of the peptide chains, controlling the formation of nanofibrils.
Article
Chemistry, Multidisciplinary
Chao Dong, Guangqi Wu, Chen Chen, Xia Li, Rui Yuan, Liang Xu, Hui Guo, Jay Zhang, Hua Lu, Feng Wang
Summary: Researchers have developed a novel biocompatible selenopolypeptide and site-specifically conjugated it with A1AT, demonstrating that this strategy can improve the pharmacological properties of A1AT and potentially be applied to other oxidation-sensitive biotherapeutics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Chenglong Ge, Junliang Zhu, Guangqi Wu, Huan Ye, Hua Lu, Lichen Yin
Summary: This study introduces a novel design of selenium-containing polypeptides that exhibit high sensitivity to reactive oxygen species (ROS) and show promising potential in drug delivery for cancer treatment.
Article
Polymer Science
Chong Zhang, Hua Lu
Summary: Synthetic polypeptides, or poly(alpha-amino acid)s (P alpha AAs), are biomimetic and biodegradable polymers that hold great promise for various biomedical applications. This article reviews the recent advances in the use of alpha-helical polypeptides for biomedical purposes, focusing on the manipulation of dynamic transitions, conformation-associated anti-biofouling coatings, cellular uptake regulation, and reducing immunogenicity of polypeptide-protein conjugates. The article also discusses the challenges and future directions in this field.
CHINESE JOURNAL OF POLYMER SCIENCE
(2022)
Article
Multidisciplinary Sciences
Yali Hu, Zi-You Tian, Wei Xiong, Dedao Wang, Ruichi Zhao, Yan Xie, Yu-Qin Song, Jun Zhu, Hua Lu
Summary: This study presents a water-assisted controlled ring-opening polymerization method for ProNCA, which enables the rapid synthesis of well-defined PLP in a short time. The use of water facilitates proton shift and lowers the energy barrier, leading to fast and efficient reactions. The protein-mediated ROP of ProNCA offers a convenient approach for the synthesis of various protein-PLP conjugates with enhanced properties.
NATIONAL SCIENCE REVIEW
(2022)
Article
Chemistry, Multidisciplinary
Jianhua Lu, Zhun Xu, Hailin Fu, Yao Lin, Huan Wang, Hua Lu
Summary: The protein-mediated, aggregation-induced polymerization of amphiphilic LPA-derived monomers at room temperature enables low concentration PDS conjugation and enhances protein stability and resistance to enzymatic activity and freeze-thaw treatments. It also allows rapid purification of Cys-bearing proteins and opens up new possibilities for protein delivery, reversible protein engineering, enzyme preservation, and recycling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Engineering, Biomedical
Meng Yang, Zheng-Chu Zhang, Fu-Zhen Yuan, Rong-Hui Deng, Xin Yan, Feng-Biao Mao, You-Rong Chen, Hua Lu, Jia-Kuo Yu
Summary: Osteochondral injury is a common orthopedic disease that can result in degenerative joint disease. Tissue engineering has potential for osteochondral repair, but implanted scaffolds often cause unwanted immune reactions. In this study, a polypeptide-based hydrogel was prepared with suitable biodegradability, excellent biocompatibility, and low immunogenicity. It showed optimal performance for osteochondral repair in rabbits, even at the early stage of implantation. Further studies confirmed its immunomodulatory role in inducing minimal foreign body reactions and promoting immunosuppressive macrophage polarization.
BIOACTIVE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Zhuanglin Shen, Yiming Sun, Guoliang Zhu, Gaixia Xu, Zhenqiang Yu, Hua Lu, Yantao Chen
Summary: Attaching polymers, particularly polyethylene glycol (PEG), to protein drugs can extend their circulation time in the bloodstream. However, the use of a helical polyglutamate as a conjugate may challenge this theoretical framework. In this study, molecular simulations were used to investigate the structure-activity relationships of P(EG3Glu)-IFN conjugates. The results suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein-polymer conjugates.
Article
Polymer Science
Shuo Wang, Hua Lu
Summary: This study reports a method for synthesizing thiol-functionalized polypeptides, which successfully suppresses the intramolecular isomerization side reactions and achieves homo-and copolypeptides with improved yield, high molecular weight, and narrow molecular weight distributions by selecting appropriate reaction solvents and adding benzoic acid as an additive. In addition, successful postpolymerization modifications of the D-Pen-containing copolypeptides on the tertiary thiols are achieved with high efficiency through thiol-Michael, SN2, and nitrosylation reactions. This work provides an efficient protection-free approach to generating functional polypeptides and creates a fundamental understanding for Pen-NCA chemistry.
Article
Polymer Science
Yi Zhang, Hua Lu
Summary: Ring-opening copolymerization is an important method to combine the properties of different monomers and adjust polymer properties. However, the copolymerization of two different monomers with full recyclability is rare. In this study, we successfully copolymerized rigid 4-hydroxyproline-derived thiolactone with various lipoic acid derivatives with flexible backbones to prepare poly(thioester-co-disulfide) copolymers with tunable thermal and mechanical properties. The resulting copolymers can be depolymerized to high monomer yields for full recycling. This research provides a detailed understanding of the kinetics and controllability of the thiolactone and 1,2-dithiolane copolymerization system, which may contribute to the design, modification, and strengthening of new recyclable polymer materials in the future.
Article
Polymer Science
Helen Yao, Kai Sheng, Jialing Sun, Shupeng Yan, Yingqin Hou, Hua Lu, Bradley D. Olsen
Article
Chemistry, Physical
Dongxiao Yin, Hao Wen, Guangqi Wu, Shaolu Li, Chenyang Liu, Hua Lu, Dehai Liang
Article
Polymer Science
Wei Xiong, Chong Zhang, Xiaolin Lyu, Hantao Zhou, Wenying Chang, Yu Bo, Erqiang Chen, Zhihao Shen, Hua Lu
