IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-03 DOI: 10.1002/cbic.202500268

Carson Cole, Brett H Pogostin, Vardan H Vardanyan, Kiana A Cahue, Thi H Bui, Adam C Farsheed, Joseph W R Swain, Jonathan Makhoul, Marija Dubackic, Peter Holmqvist, Ulf Olsson, Anatoly B Kolomeisky, Kevin J McHugh, Jeffrey Dale Hartgerink

{"title":"Covalent Stabilization of Collagen Mimetic Triple Helices and Assemblies by Dopa Crosslinking.","authors":"Carson Cole, Brett H Pogostin, Vardan H Vardanyan, Kiana A Cahue, Thi H Bui, Adam C Farsheed, Joseph W R Swain, Jonathan Makhoul, Marija Dubackic, Peter Holmqvist, Ulf Olsson, Anatoly B Kolomeisky, Kevin J McHugh, Jeffrey Dale Hartgerink","doi":"10.1002/cbic.202500268","DOIUrl":"https://doi.org/10.1002/cbic.202500268","url":null,"abstract":"Creating thermally stable collagen mimetic peptides (CMPs) is a persistent challenge. Nature leverages covalent crosslinkings to stabilize collagen's triple helix and higher-order assemblies. Herein, we demonstrate that crosslinkings between levodopa (Dopa) and lysine can covalently stabilize the triple helix in collagen mimetic peptides. Since alkaline conditions catalyze the oxidation of the catechol on Dopa to a benzoquinone, while being in proximity to the nucleophilic lysine, we hypothesized that this reaction could be a facile method to covalently capture the supramolecular structure of CMPs by simply increasing the pH of the aqueous solvent with the addition of sodium hydroxide. This strategy covalently stabilizes CMP homotrimers and a de novo designed ABC-type heterotrimer demonstrating that the Lysine-Dopa covalent bond is best templated by a supramolecular, axial cation-π pairwise interaction. In nature, collagen can hierarchically assemble into fibers. This behavior can be mimicked with the self-assembly of CMPs, but the resulting nanofibers typically exhibit thermal stability below body temperature. In a final application, we demonstrate that Dopa-Lysine covalent capture also enhances the thermal stability of CMP nanofibers well above 37 °C. This biomimetic covalent capture strategy can stabilize a wide variety of CMP systems and potentially enable the biomedical application of these materials.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500268"},"PeriodicalIF":2.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adding a C-terminal amino acid prevents the conformational interconversion of plecanatide analogues. 添加一个c端氨基酸可以阻止多聚糖类似物的构象相互转换。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-02 DOI: 10.1002/cbic.202500237

Guiyang Yao, Yi Zhou, Jingyan Jin, Pingzheng Zhou, Wu Su

引用次数: 0

Exploring the Substrate Flexibility of GrsB Thioesterase Leads to the Structural Reassignment of a Gramicidin S Variant. 探索GrsB硫酯酶的底物灵活性导致Gramicidin S变体的结构重分配。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-02 DOI: 10.1002/cbic.202500412

Sho Konno, Tomoe Mizuguchi, Atsuko Suzuki, Miyu Tanaka, Fumihiro Ishikawa, Akihiro Taguchi, Atsuhiko Taniguchi, Genzoh Tanabe, Yoshio Hayashi

{"title":"Exploring the Substrate Flexibility of GrsB Thioesterase Leads to the Structural Reassignment of a Gramicidin S Variant.","authors":"Sho Konno, Tomoe Mizuguchi, Atsuko Suzuki, Miyu Tanaka, Fumihiro Ishikawa, Akihiro Taguchi, Atsuhiko Taniguchi, Genzoh Tanabe, Yoshio Hayashi","doi":"10.1002/cbic.202500412","DOIUrl":"https://doi.org/10.1002/cbic.202500412","url":null,"abstract":"Gramicidin S (GS) is a cyclic decapeptide derived from two pentapeptides. The C-terminal thioesterase (TE) domain of gramicidin S synthetase B (GrsB) dimerizes precursor pentapeptides and cyclizes the resulting linear decapeptide. Recently, a GS variant (GS-SA), in which a single D-Phe was replaced by L-Ser(Allyl), was reported via precursor-directed biosynthesis in a native GS producer. To understand how GrsB-TE processes such modified precursors, we investigated its substrate specificity using synthetic linear peptides. GrsB-TE cyclized a substrate containing L-Ser(Allyl) at position 6 but not at position 1. However, the enzymatically synthesized GS-SA showed a different HPLC retention time than that of the reported GS variant. Further structural and functional analyses, including 1H NMR, antimicrobial assays, and circular dichroism spectroscopy, revealed that the reported GS-SA contained D-Ser(Allyl) rather than L-Ser(Allyl). These findings reveal a previously unrecognized stereochemical flexibility in GrsB-TE and support the structural revision of the reported GS variant.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500412"},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient Biosynthesis of Polyhydroxybutyrate from Xylose via an In Vitro Synthetic Enzymatic Biosystem with Self-Sustained Cofactor Regeneration. 木糖高效生物合成聚羟基丁酸的体外合成酶生物系统与自我维持的辅因子再生。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-02 DOI: 10.1002/cbic.202500387

Boyu Qiu, Xinlei Wei, Chun You

{"title":"Efficient Biosynthesis of Polyhydroxybutyrate from Xylose via an In Vitro Synthetic Enzymatic Biosystem with Self-Sustained Cofactor Regeneration.","authors":"Boyu Qiu, Xinlei Wei, Chun You","doi":"10.1002/cbic.202500387","DOIUrl":"https://doi.org/10.1002/cbic.202500387","url":null,"abstract":"In vitro biotransformation (ivBT) mediated by in vitro synthetic enzymatic biosystems (ivSEBs) represents a highly promising platform for sustainable biomanufacturing, offering enhanced reaction efficiency by circumventing cellular constraints. In this study, we developed an ivSEB comprising 17 enzymes for the cell-free biosynthesis of polyhydroxybutyrate (PHB) from D-xylose via the acetyl-coenzyme A. This ivSEB integrates partial glycolysis and the pentose phosphate pathway, enabling self-sustained balance of several cofactors including coenzyme A (CoA), NADP+/NADPH and ATP/ADP. Stoichiometric analysis demonstrated a theoretical molar yield of PHB from xylose of 111.1%. Through optimizing concentrations of cofactors and enzymes, the one-pot reaction produced 44.0 mM (3.8 g/L) PHB from 44.8 mM (6.7 g/L) xylose, corresponding to a molar yield of 98.2%. Even at a higher substrate concentration (13.5 g/L), the yield remained robust (84.5%). This study demonstrated the potential of ivSEB as a scalable and efficient approach for the large-scale production of PHB and other xylose-based or acetyl-CoA-derived chemicals.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500387"},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photo-triggered Hyaluronic Acid Hydrogel for 3D Culture and Cell Recovery. 光触发透明质酸水凝胶用于三维培养和细胞恢复。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-02 DOI: 10.1002/cbic.202500310

Francesco Palmieri, Marième Gueye, Lucía Vicario Del Rio, Saskia Bunschuh, Pradeep Chopra, Silvia Mihăilă, Tina Vermonden, Riccardo Levato, Geert-Jan Boons

{"title":"Photo-triggered Hyaluronic Acid Hydrogel for 3D Culture and Cell Recovery.","authors":"Francesco Palmieri, Marième Gueye, Lucía Vicario Del Rio, Saskia Bunschuh, Pradeep Chopra, Silvia Mihăilă, Tina Vermonden, Riccardo Levato, Geert-Jan Boons","doi":"10.1002/cbic.202500310","DOIUrl":"https://doi.org/10.1002/cbic.202500310","url":null,"abstract":"Properties of semi-synthetic hydrogels can be fine-tuned making these attractive for various applications in regenerative medicine. Here, we describe a hydrogel platform based on hyaluronic acid (HA) modified by (1R,8S,9S)-bicycle[6.1.0]non-4-yn-9-ylmethanol (BCN) and a cross-linker composed of light sensitive o-nitrobenzyl and polyethylene glycol (PEG) chains terminating in azides. The two components can undergo strain-promoted azide-alkyne cycloaddition (SPAAC) resulting in rapid gel formation. First, we incorporated adipose-derived mesenchymal stromal cells (aMSCs) in the hydrogel and demonstrated that the cells can be easily retrieved by UV light mediated degradation maintaining viability and retaining spindle-like shape when the cells were replated. Next, we provided a proof-of-concept of inducing light-mediated softening of the hydrogel to modulate the morphology of the encapsulated cells. A co-culture of endothelial cells (cord blood-derived endothelial colony forming cells (ECFCs) and bone marrow derived mesenchymal stromal cells (bmMSCs), which are commonly studied for their ability to form capillary-like vascular networks, were cultured in the regular and light induced softened hydrogels. Non-photoexposed hydrogels showed cells with a prevalently rounded morphology, whereas stretched cells connecting into a primitive capillary network were observed in the light-softened hydrogels. Photo-induced softening offers potential to locally control cell shape and self-organization capacity.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500310"},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Matrix-Assisted Efficient Selection of a High-Affinity Circular Aptamer for Sensitive Detection of Low-Density Lipoprotein in Human Serum. 基质辅助筛选高亲和力圆形适体灵敏检测人血清低密度脂蛋白。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-01 DOI: 10.1002/cbic.202500059

Long Sun, Yuefei Zhou, Jie Wang, Lili Yao, Hao Qu, Yu Mao, Lei Zheng

{"title":"Matrix-Assisted Efficient Selection of a High-Affinity Circular Aptamer for Sensitive Detection of Low-Density Lipoprotein in Human Serum.","authors":"Long Sun, Yuefei Zhou, Jie Wang, Lili Yao, Hao Qu, Yu Mao, Lei Zheng","doi":"10.1002/cbic.202500059","DOIUrl":"https://doi.org/10.1002/cbic.202500059","url":null,"abstract":"The accurate and rapid detection of human serum biomakers is crucial for the early diagnosis of related diseases. Circular aptamers emerge as promising candidates for the precise recognition of these biomakers due to their remarkable biological and structural stability. In this study, we successfully identified a high-affinity circular DNA aptamer for Low-density lipoprotein (LDL), a key biomarker for cardiovascular diseases, through matrix-assisted efficient selection strategy conducted directly in human serum. This circular aptamer demonstrated a dissociation constant (Kd) as low as 18 nM and exhibited exceptional specificity for LDL, showing negligible responses to closely related analogs such as high-density lipoprotein and other abunzaidant human serum substances. We subsequently developed a sensitive aptasensor that utilizes the superior recognition capability of the circular DNA aptamer, which performed well even in human serum (with a limit of detection down to 0.4 μM and a wide linear concentration range of three orders of magnitude). This work underscores the feasibility of rapidly isolating highly functional circular DNA aptamers in one selection round, thereby accelerating the discovery of various circular DNA aptamers that are well-suited for molecular recognition of a wide array of emerging human serum biomarkers.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500059"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coordination Polymer Carrying Antimicrobial Peptide for Enhanced Anti-Infective Therapy. 携带抗菌肽的配位聚合物增强抗感染治疗。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-30 DOI: 10.1002/cbic.202500286

Madiha Saqlain, Hafiz Muhammad Zohaib, Dilawar Akram, Samina Qamar, Iqra Tabassum, Muhammad Irfan, Hui Li

{"title":"Coordination Polymer Carrying Antimicrobial Peptide for Enhanced Anti-Infective Therapy.","authors":"Madiha Saqlain, Hafiz Muhammad Zohaib, Dilawar Akram, Samina Qamar, Iqra Tabassum, Muhammad Irfan, Hui Li","doi":"10.1002/cbic.202500286","DOIUrl":"https://doi.org/10.1002/cbic.202500286","url":null,"abstract":"Antimicrobial peptides (AMPs) offer a promising avenue for combating drug-resistant bacterial infections, but their clinical utility is often limited by poor bioavailability and stability. This study presents the design and synthesis of a novel, enantiomerically pure 2D-coordination polymer, {[Cu(dUMP)(dpp)2]·3(H2O)·(NO3)]}n (CP-1), derived from Cu(II) ions, deoxy-uridine monophosphate, and 1,3-di(4-pyridyl)propane (dpp), as a potential delivery system for AMPs. Single-crystal X-ray diffraction reveals a 2D double helical structure with square pyramidal Cu(II) coordination. Spectroscopic characterization (IR, UV-vis, thermogravimetric analysis, X-ray diffraction, circular dichroism) confirms the successful synthesis and reveals chirality transfer to the achiral dpp ligand. Molecular docking studies identify DGL 13K as the AMP exhibiting the strongest binding affinity to CP-1 (ΔG = -13.03 kcal mol-1). Critically, molecular dynamics simulations provide detailed insights into the mechanism of action of the CP-1-DGL 13K complex against a Gram-negative bacterial membrane. The simulations demonstrate that DGL 13K, stabilized by CP-1, undergoes conformational changes, penetrating the membrane and disrupting its integrity through pore formation. These findings highlight the potential of CP-1 as an effective carrier for AMPs, enhancing their stability and facilitating membrane disruption, offering a promising strategy for developing novel antimicrobial therapies to combat drug resistance.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500286"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Antibody-Based Strategies for Targeted Degradation of Membrane and Extracellular Proteins. 基于抗体的膜和细胞外蛋白靶向降解策略的发展。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-30 DOI: 10.1002/cbic.202500184

Xiaoqing Cai, Huanhuan Sun, Na Li

{"title":"Development of Antibody-Based Strategies for Targeted Degradation of Membrane and Extracellular Proteins.","authors":"Xiaoqing Cai, Huanhuan Sun, Na Li","doi":"10.1002/cbic.202500184","DOIUrl":"https://doi.org/10.1002/cbic.202500184","url":null,"abstract":"Membrane and extracellular proteins are essential components in various biological processes that ensure cellular function and homeostasis. Their dysregulation is linked to a wide range of diseases, making them pivotal therapeutic targets. Recent innovations in therapeutic strategies have concentrated on targeted protein degradation, particularly via the endocytosis-lysosome pathway, offering a novel approach to restoring balance within cellular systems. This review elucidates recent advancements in antibody-based therapeutics designed for the targeted degradation of membrane and extracellular proteins, specifically emphasizing three key mechanisms: lysosomal targeting receptors, transmembrane E3 ligases, and lysosome-sorting signals that facilitate the degradation of disease-relevant proteins. We focus on various construction strategies for these antibody-based therapeutics, highlighting the potential of antibody-ligand conjugates, bispecific antibodies, and antibody fusion proteins. By leveraging the natural endocytic pathway for efficient protein internalization and subsequent lysosomal degradation, these antibody-based platforms hold significant promise for developing targeted therapies for a variety of diseases. Through this review, we aim to provide insights into the exciting field of antibody-enabled lysosomal degradation and its implications for future therapeutic interventions.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500184"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemically Synthesized LRAD3-D1 Interacts with N-terminal Domain of SARS-CoV-2 Spike Protein. 化学合成的LRAD3-D1与SARS-CoV-2刺突蛋白n端结构域相互作用

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-29 DOI: 10.1002/cbic.202500403

Mrinmoy Jana, Rathina Delipan, Arighna Sarkar, Sreejith R Raran-Kurussi, Rajesh P Ringe, Kalyaneswar Mandal

{"title":"Chemically Synthesized LRAD3-D1 Interacts with N-terminal Domain of SARS-CoV-2 Spike Protein.","authors":"Mrinmoy Jana, Rathina Delipan, Arighna Sarkar, Sreejith R Raran-Kurussi, Rajesh P Ringe, Kalyaneswar Mandal","doi":"10.1002/cbic.202500403","DOIUrl":"https://doi.org/10.1002/cbic.202500403","url":null,"abstract":"Growing evidence of post-COVID neurological complications, such as encephalopathy, neurodegeneration, and cognitive impairment, suggests SARS-CoV-2 viral infection into the central nervous system (CNS). Therefore, understanding the mechanisms of viral entry into the CNS, where human angiotensin-converting enzyme 2 is barely expressed, is critical for addressing the neurological consequences of COVID-19. Importantly, the low-density lipoprotein receptor class A domain containing 3 (LRAD3) is overexpressed in brain cells, suggesting a possible ACE2-independent alternate pathway of viral entry into brain cells. Herein, we report the interaction of the chemically synthesized LRAD3 domains with SARS-CoV-2 spike protein. We observed that the extracellular domains of LRAD3 depend on calcium for proper folding and maintaining their structural integrity. Our results revealed that domain 1 of LRAD3, which is most accessible from the cell surface, engages with the N-terminal domain of the viral spike protein. These findings open up possibilities to develop new therapeutic strategies targeting ACE2 independent viral entry pathways.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500403"},"PeriodicalIF":2.6,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

5-thiohistidine N-acetyltransferase from Proteiniphilum saccharofermentans. 糖化蛋白的5-硫代组氨酸n -乙酰转移酶。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-26 DOI: 10.1002/cbic.202400439

Cangsong Liao, David Lim, Gladwin Suryatin Alim, Florian P Seebeck

引用次数: 0

ChemBioChem最新文献