Article
Chemistry, Multidisciplinary
George J. Saunders, Andrei K. Yudin
Summary: The passive membrane permeability of macrocycles can be greatly improved by incorporating heterocyclic grafts. However, the permeability does not scale linearly with the number of heterocycles, highlighting the subtleties of the conformation-property relationship in this class of molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Engineering, Biomedical
Jinkyu Lee, Seung Jae Huh, Ji Min Seok, Sangmin Lee, Hayeon Byun, Gyu Nam Jang, Eunhyung Kim, Se-jeong Kim, Su A. Park, Sung Min Kim, Heungsoo Shin
Summary: In this study, we developed 3D printed scaffolds with bioactive surfaces coated with minerals and platelet-derived growth factors. The results showed that the mineral deposition and compressive modulus on the scaffold surface were enhanced, and the immobilization of PDGF further promoted osteogenic differentiation and the secretion of pro-angiogenic factors. In vivo experiments on mice demonstrated that the scaffold significantly improved bone regeneration and neovessel formation.
ACTA BIOMATERIALIA
(2022)
Review
Biochemistry & Molecular Biology
Tristan J. Tyler, Thomas Durek, David J. Craik
Summary: Bioactive peptides are a diverse group of molecules with varied structures and functions. However, their use as drug candidates has been limited due to inherent shortcomings, including short half-lives and poor cell permeability. This review explores the use of molecular engineering to insert bioactive sequences into constrained scaffolds with desired pharmaceutical properties. Specifically, the focus is on cyclic disulfide-rich scaffolds, either naturally derived or engineered, which are intrinsically stable and amenable to sequence modifications, making them privileged frameworks in drug design.
Article
Cell & Tissue Engineering
Nupur Kohli, Vaibhav Sharma, Alodia Orera, Prasad Sawadkar, Nazanin Owji, Oliver G. Frost, Russell J. Bailey, Martyn Snow, Jonathan C. Knowles, Gordon W. Blunn, Elena Garcia-Gareta
Summary: This study aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties for bone tissue engineering applications. The materials were characterized as porous with evenly distributed deposits of CaP precursor phases, which facilitated cell adhesion, proliferation, migration, and differentiation down the osteogenic pathway. In addition, results from the CAM assay showed that the scaffolds were pro-angiogenic and biocompatible, highlighting their potential for further pre-clinical research prior to clinical translation.
JOURNAL OF TISSUE ENGINEERING
(2021)
Review
Biochemistry & Molecular Biology
Rafael Gonzalez-Castro, Miguel A. Gomez-Lim, Fabien Plisson
Summary: This review discusses the characteristics, stability, and applications of CRPs in protein engineering, as well as the successes and limitations of seven CRPs scaffolds and the resulting grafted peptides.
Article
Engineering, Biomedical
Marta Monguio-Tortajada, Cristina Prat-Vidal, Miriam Moron-Font, Marta Clos-Sansalvador, Alexandra Calle, Paloma Gastelurrutia, Adriana Cserkoova, Anna Morancho, Miguel Angel Ramirez, Anna Rosell, Antoni Bayes-Genis, Carolina Galvez-Monton, Francesc E. Borras, Santiago Roura
Summary: The study presents a novel MSC-EV delivery approach for cardiac repair, showing significant effects in reducing immune response, promoting angiogenesis, and reducing inflammation. The research demonstrates the potential therapeutic efficacy of loading EV in engineered pericardial scaffolds for treating myocardial infarction.
BIOACTIVE MATERIALS
(2021)
Article
Biochemical Research Methods
Kuok Yap, Junqiao Du, Fabian B. H. Rehm, Shyn Ric Tang, Yan Zhou, Jing Xie, Conan K. Wang, Simon J. de Veer, Linda H. L. Lua, Thomas Durek, David J. Craik
Summary: The protocol outlines a method for producing cyclic peptide precursors in Pichia pastoris that can be enzymatically matured into cyclic peptides, suitable for drug development and biotechnology applications. The process is versatile, allowing for the generation of cyclic peptides of varying classes and sizes, with production and purification taking approximately 24 days.
Article
Chemistry, Multidisciplinary
Colin N. Kelly, Chad E. Townsend, Ajay N. Jain, Matthew R. Naylor, Cameron R. Pye, Joshua Schwochert, R. Scott Lokey
Summary: This study focused on investigating the structure-permeability relationships in lariat peptides, which are cyclized from one termini onto a side chain. A library of over 1000 novel lariat peptide scaffolds with molecular weights around 1000 was generated using stable isotopes to encode stereochemistry. The research found that passive permeability of lariat peptides was strongly dependent on N-methylation, stereochemistry, and ring topology, revealing various trends in structure-permeability relationships.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Medicinal
Amy L. Thomson, Andrea J. Robinson, Alessia Belgi
Summary: Recombinant peptide synthesis allows for mass production of therapeutically potential peptides, but the synthesis of dicarba peptidomimetics becomes challenging due to the Lewis basicity of amine and sulfur-containing residues. This study presents a combination of strategies to deactivate coordinative residues and achieve efficient Ru-catalyzed ring-closing metathesis. The method was demonstrated using α-conotoxin EpI, a disulfide-containing sequence, by replacing the disulfide loop with E/Z-dicarba bridges.
Article
Chemistry, Multidisciplinary
Rita I. R. Ibanez, Ronaldo J. F. C. do Amaral, Christopher R. Simpson, Sarah M. Casey, Rui L. Reis, Alexandra P. Marques, Ciara M. Murphy, Fergal J. O'Brien
Summary: This study successfully incorporated PRP into a bioink for 3D printing regenerative scaffolds with controlled release of growth factors, showing superior angiogenic potential without inducing myofibroblastic phenotype in fibroblasts. This disruptive technology allows for personalized treatment with enhanced vascularization in tissue engineering applications.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Polymer Science
Gustavo A. Rico-Llanos, Sara Borrego-Gonzalez, Miguelangel Moncayo-Donoso, Jose Becerra, Rick Visser
Summary: Collagen type I is widely used in bone tissue engineering due to its excellent biocompatibility and osteoconductivity, but it also has drawbacks such as high biodegradability and low mechanical strength. Recent efforts have been focused on designing and producing collagen implants to enhance bone regeneration.
Article
Chemistry, Medicinal
Christian R. O. Bartling, Flora Alexopoulou, Sarah Kuschert, Yanni K. -Y. Chin, Xinying Jia, Vita Sereikaite, Dennis Ozcelik, Thomas M. Jensen, Palash Jain, Mads M. Nygaard, Kasper Harpsoe, David E. Gloriam, Mehdi Mobli, Kristian Stromgaard
Summary: Peptides targeting disease-relevant protein-protein interactions have limitations in terms of metabolic stability and membrane permeability. Peptide cyclization, particularly hydrocarbon stapling, offers a valuable approach to develop metabolically stable and cell-permeable cyclic leads with improved affinity and stability. In this study, a comprehensive examination of cyclization strategies led to the identification of cyclic APP dodecamer peptides that target the phosphotyrosine binding domain of Mint2 with significantly improved properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Lei Wang, Meng Xu, Haofeng Hu, Lun Zhang, Fei Ye, Jia Jin, Hongming Fang, Jian Chen, Guiqian Chen, Sylvain Broussy, Michel Vidal, Zhengbing Lv, Wang-Qing Liu
Summary: The study identified a cyclic peptide, B-cL1, which effectively inhibited the interaction between VEGF/VEGFR, showing anti-angiogenic and anti-tumoral effects. This peptide could serve as a lead for designing new and more potent VEGFR antagonists for angiogenesis-related diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Qian Yu Liu, Guo Wen Sun, Jiang Long Pan, Shi Kun Wang, Chao Yue Zhang, Yan Chun Wang, Xiu Ping Gao, Geng Zhi Sun, Zhen Xing Zhang, Xiao Jun Pan, Jin Yuan Zhou
Summary: Defect-rich MoS2-x nanosheet/ZnS nanoparticle heterojunction composites were successfully synthesized using a one-pot metal ion cutting-assisted method. The resulting cathodes showed high reversible capacity and exceptional cycling stability as sulfur hosts for lithium-sulfur batteries. The MoS2-x nanosheets improved the chemisorption and catalytic kinetic process of redox reactions, while the heterojunctions with ZnS nanoparticles accelerated electron transport and Li+ ion diffusion.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Chemistry, Physical
Tingting Liu, Na Peng, Xikun Zhang, Runtian Zheng, Maoting Xia, Haoxiang Yu, Miao Shui, Ying Xie, Jie Shu
Summary: This study employs defect chemistry to control the defect engineering of TiS2 materials, introducing sulfur vacancies to improve their electrochemical performance, including cycling ability and dynamic characteristics. The concentration and species of defects can be controlled by adjusting experimental conditions, and the enhancement of electrochemical performance is closely related to the concentration of defects.
Article
Chemistry, Medicinal
Xiaopeng Zhu, Shuai Wang, Quentin Kaas, Jinpeng Yu, Yong Wu, Peta J. Harvey, Dongting Zhangsun, David J. Craik, Sulan Luo
Summary: The researchers characterized a novel alpha-conotoxin, LvIC, and its analogues to probe structure-activity relationships at the alpha 6 beta 4 nAChR. They found a potent and specific antagonist, [D1G,delta Q14]LvIC, which could potentially serve as a novel molecular probe to explore alpha 6 beta 4 nAChR-related neurophysiological and pharmacological functions.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Isabella R. Palombi, Nicole Lawrence, Andrew M. White, Caitlin L. Gare, David J. Craik, Brendan J. McMorran, Lara R. Malins
Summary: Targeted drug delivery with peptide-drug conjugates (PDCs) was investigated as an alternative antimalarial therapy. PDCs with low micromolar potency were developed by conjugating a synthetic peptide derived from an innate human defense molecule with the antimalarial drug primaquine (PQ). Various PDCs were designed to identify the optimal conjugation site and investigate linker length, hydrophilicity, and cleavability. Conjugation within a flexible spacer region of the peptide, with a cleavable linker to liberate the PQ cargo, was crucial for retaining the activity of both the peptide and drug.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemical Research Methods
Qiushi Cao, Cheng Ge, Xuejie Wang, Peta J. Harvey, Zixuan Zhang, Yuan Ma, Xianghong Wang, Xinying Jia, Mehdi Mobli, David J. Craik, Tao Jiang, Jinbo Yang, Zhiqiang Wei, Yan Wang, Shan Chang, Rilei Yu
Summary: With the rise of multidrug-resistant bacteria, antimicrobial peptides (AMPs) have emerged as potential alternatives to traditional antibiotics for treating bacterial infections. However, traditional methods of discovering and designing AMPs are time-consuming and costly. This study utilized deep learning techniques, including sequence generative adversarial nets, bidirectional encoder representations from transformers, and multilayer perceptron, to design and identify AMPs. Six candidate AMPs were then screened and one of them, A-222, showed inhibition against both gram-positive and gram-negative bacteria. Structural analysis and subsequent structure-activity relationship studies led to the design of peptide analogs with increased activity against specific bacteria. Overall, deep learning holds great promise in accelerating the discovery of novel AMPs and could have significant implications in developing new antimicrobial treatments.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemistry & Molecular Biology
Xiaorong Liu, Sonia T. Henriques, David J. Craik, Lai Yue Chan
Summary: This article introduces Gomesin, a cationic antimicrobial peptide isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana and can be chemically produced. Gomesin exhibits a range of biological activities against therapeutically relevant pathogens and has been used for drug design and development. The review provides an overview of the discovery, structure-activity relationships, mechanism of action, biological activity, and potential clinical applications of Gomesin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zitong Zhao, Teng Pan, Shen Chen, Peta J. Harvey, Jinghui Zhang, Xiao Li, Mengke Yang, Linhong Huang, Shoushi Wang, David J. Craik, Tao Jiang, Rilei Yu
Summary: mu-Conotoxin KIIIA is a selective blocker of sodium channels with strong inhibitory activity against Nav1.7. Its structural modification and synthesis are challenging due to the presence of three pairs of disulfide bonds. In this study, three KIIIA analogues with one disulfide bond deleted were designed and synthesized. Among them, analogue KIIIA-1 showed the highest inhibitory activity on hNav1.7. A computational model was used to determine its binding pattern to hNav1.7 and guide the design of second and third-generation analogues. Peptide 37, the most potent analogue, exhibited significantly improved inhibitory activity on hNav1.7 and demonstrated potent analgesic effects in an in vivo pain model.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Plant Sciences
Joanne T. Blanchfield, Maribel G. Nonato, Richard J. Clark
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Plant Sciences
Abhishek Bajpai, Mark A. Jackson, Yen-Hua Huang, Kuok Yap, Qingdan Du, Tevin Chui-Ying Chau, David J. Craik, Edward K. Gilding
Summary: Cyclotides are stable and cyclic mini-proteins found in plants, which have nematicidal and anthelmintic activities. Extracts from four major cyclotide-producing plants were tested for their nematicidal properties and were found to be effective against Caenorhabditis elegans. The isolated cyclotides caused damage to the worms' mouth, pharynx, and midgut or membrane, and membrane disruption was implicated in their toxicity and death. The results provide a simple assay design to explore the nematicidal activities of plant extracts and purified cyclotides on C. elegans.
JOURNAL OF NATURAL PRODUCTS
(2023)
Review
Chemistry, Medicinal
Linh T. T. Nguyen, David J. J. Craik, Quentin Kaas
Summary: The venom of marine cone snails contains peptide toxins known as conopeptides, particularly conotoxins that are rich in disulfide bonds. Previous publications have mentioned the significant interest in conopeptides due to their potent and selective activity, but there has not been a formal analysis quantifying the popularity of the field. In this study, we conducted a bibliometric analysis of cone snail toxin literature from 2000 to 2022, which revealed the prolific nature of conopeptide research, with an average of 130 research articles per year.
Article
Biochemistry & Molecular Biology
Marie Morin, Mathias Joesson, Conan K. Wang, David J. Craik, Sandie M. Degnan, Bernard M. Degnan
Summary: This study investigates the impact of captivity on the physiology and health of crown-of-thorns starfish by comparing gene expression in wild and captive individuals. The results show significant differences in gene expression between wild and captive starfish, with genes involved in oxidative stress and energy metabolism upregulated in captivity. This suggests that caution should be taken when extrapolating results from captive marine animals to their wild counterparts.
Review
Biochemistry & Molecular Biology
Tristan J. Tyler, Thomas Durek, David J. Craik
Summary: Bioactive peptides are a diverse group of molecules with varied structures and functions. However, their use as drug candidates has been limited due to inherent shortcomings, including short half-lives and poor cell permeability. This review explores the use of molecular engineering to insert bioactive sequences into constrained scaffolds with desired pharmaceutical properties. Specifically, the focus is on cyclic disulfide-rich scaffolds, either naturally derived or engineered, which are intrinsically stable and amenable to sequence modifications, making them privileged frameworks in drug design.
Article
Biochemical Research Methods
Mark A. A. Jackson, Jing Xie, Linh T. T. Nguyen, Xiaohan Wang, Kuok Yap, Peta J. J. Harvey, Edward K. K. Gilding, David J. J. Craik
Summary: Multiple sclerosis (MS) is a debilitating disease that requires prolonged treatment. The experimental therapeutic [T20K]kB1, a mutant of a plant peptide, shows promise for oral dosing and stability due to its cyclic structure. This study demonstrates the production of [T20K]kB1 in the Nicotiana benthamiana plant, providing a sustainable and cost-effective production method for cyclotide-based therapeutics.
TRANSGENIC RESEARCH
(2023)
Article
Immunology
Zhian Chen, Yanfang Cui, Yin Yao, Bo Liu, Joseph Yunis, Xin Gao, Naiqi Wang, Pablo F. Canete, Zewen Kelvin Tuong, Hongjian Sun, Hao Wang, Siling Yang, Runli Wang, Yew Ann Leong, David Simon Davis, Jiahuan Qin, Kaili Liang, Jun Deng, Conan K. Wang, Yen-Hua Huang, Jonathan A. Roco, Sam Nettelfield, Huaming Zhu, Huajun Xu, Zhijia Yu, David Craik, Zheng Liu, Hai Qi, Christopher Parish, Di Yu
Summary: In antibody responses, mutated germinal center B (BGc) cells are positively selected for reentry or differentiation, with the support of TFH cell-derived signals including CD40 and IL-21. The binding and signaling of IL-21 in BGc cells is reduced compared to non-BGc cells, due to low cellular heparan sulfate (HS) sulfation. Ndst1-mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength, and selective desensitization to IL-21 occurs in BGc cells. Therefore, the biochemical regulation of IL-21 availability and signal strength plays a crucial role in GC selection.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jan Philipp Menzel, Reuben S. E. Young, Aurelie H. Benfield, Julia S. Scott, Puttandon Wongsomboon, Lukas Cudlman, Josef Cvacka, Lisa M. Butler, Sonia T. Henriques, Berwyck L. J. Poad, Stephen J. Blanksby
Summary: This study introduces a workflow for discovering new fatty acids, which adds more than 100 fatty acids to the human lipidome. The traditional methods often fail to detect the isomers of unsaturated fatty acids. By coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds, this workflow enables the rapid identification of fatty acids in complex media and even in instances of incomplete chromatographic separation. The application of this method can reveal changes in lipid metabolism.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Edin Muratspahic, Despoina Aslanoglou, Andrew M. White, Claudia Draxler, Xaver Kozisek, Zara Farooq, David J. Craik, Peter J. McCormick, Thomas Durek, Christian W. Gruber
Summary: In this study, peptide ligands for MC4R were designed using a peptide drug design approach. The designed peptides fully activated MC4R and recruited beta-arrestin-2 with higher efficacies and potencies than the endogenous alpha-MSH. These findings suggest the potential of these novel peptide ligands in developing safer and more effective antiobesity drugs.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)