ChemBioChem最新文献_第4页

NMR-Guided Fragment Screening Identifies Privileged Noncanonical Amino Acids for mRNA Display 核磁共振引导片段筛选鉴定mRNA显示的特权非规范氨基酸。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-23 DOI: 10.1002/cbic.70540

Abdul J. Castillo, Clark A. Jones, Alba C. Dutra, Chelsea A. Makovsky, Sandeep Lohan, Bipasana Shakya, Sara H. Walters, Brian Fuglestad, Matthew C. T. Hartman

{"title":"NMR-Guided Fragment Screening Identifies Privileged Noncanonical Amino Acids for mRNA Display","authors":"Abdul J. Castillo, Clark A. Jones, Alba C. Dutra, Chelsea A. Makovsky, Sandeep Lohan, Bipasana Shakya, Sara H. Walters, Brian Fuglestad, Matthew C. T. Hartman","doi":"10.1002/cbic.70540","DOIUrl":"10.1002/cbic.70540","url":null,"abstract":"Fragment-based strategies have transformed small-molecule drug discovery, yet analogous approaches for selecting noncanonical amino acids (ncAAs) in peptide drug discovery remain largely unexplored. Here we introduce an NMR-guided screening workflow that identifies individual ncAAs as “fragments” to identify privileged monomers prior to peptide library construction. Using the p53–MDM2 interaction as a benchmark system, we screened a panel of tryptophan analogs and identified 6-bromo and 6-chloro tryptophan (6Br-Trp and 6Cl-Trp) as a higher-affinity fragments relative to native Trp. Incorporation of 6Br-Trp into a model peptide improved binding to MDM2, demonstrating that amino acid affinity translates directly to peptide-level binding. We further show that 6Br-Trp and 6Cl-Trp can be efficiently charged onto tRNA and incorporated into peptides using the PURE translation system. In an mRNA display selection, peptides containing 6Br-Trp and 6Cl-Trp exhibited enhanced enrichment compared to their Trp-containing counterparts. These results show ncAA fragment screening to be a front-end strategy for guiding monomer selection in high-throughput peptide discovery via mRNA display. ncAA screening also provides a route to bias peptide libraries toward more productive chemical space to accelerate the identification of high-affinity ligands for challenging protein targets.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries 通过基因编码文库的细胞选择重新发现生物活性环肽。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-23 DOI: 10.1002/cbic.70532

Linwei Yang, Abhijit Behera, Hannah J. Meyers, Tina Wang

引用次数: 0

Tunable Design for Co-Assembly of Coiled-Coil Fibers Using Oppositely Charged Peptides 利用带相反电荷的多肽，可调设计成卷状纤维的共组装。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-23 DOI: 10.1002/cbic.70536

Austin B. Rue, Yalini Wijesundara, Erwin Kingston, Jeremiah J. Gassensmith, James A. Hebda

{"title":"Tunable Design for Co-Assembly of Coiled-Coil Fibers Using Oppositely Charged Peptides","authors":"Austin B. Rue, Yalini Wijesundara, Erwin Kingston, Jeremiah J. Gassensmith, James A. Hebda","doi":"10.1002/cbic.70536","DOIUrl":"10.1002/cbic.70536","url":null,"abstract":"Self-assembling peptide fibers have many applications, including tissue engineering, drug delivery, and environmentally friendly textile materials. However, previous studies used peptides that self-assemble, limiting their potential for large-scale synthesis. In the current study, three peptides were designed: a negatively charged 21-residue peptide (21n), a negatively charged 28-residue peptide (28n), and a positively charged 35-residue peptide (35p). Peptides of opposite charges that were exposed to each other co-assembled into α-helical coiled-coils. Peptides of different lengths allow for the formation of sticky ends, encouraging linear growth. The peptides include cysteine residues to stabilize fiber growth. Circular dichroism confirmed stable alpha-helical secondary structure, and aggregation assays were conducted to track the assembly of higher-order structures. Transmission electron microscopy was used to visually examine the aggregates that formed. When mixed, the designed peptides co-assembled into large, fibrous aggregates. These fibers were resistant to heat and salt, but they disassembled when exposed to a reducing agent such as dithiothreitol (DTT). Fibers made by pairing 21n or 28n to 35p resulted in different morphologies upon co-assembly under oxidizing conditions. Peptides that are soluble independently but co-assemble into large, disulfide-reinforced fibers present a new platform for tunable, biologically inspired fibers.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023334","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

Bottom-Up Synthesis of Artificial Cells by DNA Nanotechnology DNA纳米技术自底向上合成人工细胞

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-20 DOI: 10.1002/cbic.70526

Sunyi Tao, Yichun Xu, Junsong Han, Dayong Yang, Chi Yao, Shuo Yang, Hongjing Dou

引用次数: 0

Unspecific Peroxygenase-Based Chemo-Enzymatic Synthesis of Amino Alcohols for Pharmaceutical Preparation 基于非特异性过氧酶的化学酶合成氨基醇的药物制剂

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-20 DOI: 10.1002/cbic.70537

Simon Last, Alina Gazizova, Katharina Wittmann, Niklas Dietz, Martin J. Weissenborn, Jan von Langermann

引用次数: 0

Effects of Selenocysteine Substitution on the Cyclotide Kalata B2 硒代半胱氨酸对环肽Kalata B2的影响

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-20 DOI: 10.1002/cbic.70543

Ramoncito Luis B. de Boda, Sónia Troeira Henriques, Yen-Hua Huang, Christine C. Hernandez, Portia Mahal G. Sabido, David J. Craik

{"title":"Effects of Selenocysteine Substitution on the Cyclotide Kalata B2","authors":"Ramoncito Luis B. de Boda, Sónia Troeira Henriques, Yen-Hua Huang, Christine C. Hernandez, Portia Mahal G. Sabido, David J. Craik","doi":"10.1002/cbic.70543","DOIUrl":"https://doi.org/10.1002/cbic.70543","url":null,"abstract":"Cyclotides are peptides with a head-to-tail cyclic backbone and six cysteine residues that are linked in a knotted arrangement. Their unique structure confers exceptional stability and various biological activities, resulting in numerous studies on their synthesis and development for a range of applications. One challenge in cyclotide synthesis is the formation of the correct disulfide bonds that fold the peptide into the native conformation. Replacement of a native disulfide bond with the faster-forming diselenide bond by substituting cysteine residues with selenocysteine is a strategy that can be implemented to overcome this issue. In this study, we synthesized selenocysteine analogs of the cyclotide kalata B2 and determined the effect of the substitution on folding, structure, and biological activity. The analogs folded faster than their native counterpart, implying that the diselenide bond assists in the formation of the correct structure. HPLC and nuclear magnetic resonance (NMR) analysis revealed a native-like structure for all analogs. Cytotoxicity and membrane binding assays showed that biological activity was maintained upon selenocysteine substitution. Overall, this study demonstrates the conservative nature of diselenide replacement while improving the folding of kalata B2.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reversible Modulation of Glycan Recognition in C-Type Lectins by Calcium/Lanthanide Exchange 钙/镧系交换对c型凝集素聚糖识别的可逆调节

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-20 DOI: 10.1002/cbic.70531

Pablo Valverde, Paola Oquist-Phillips, Ángeles Canales, Ana Diniz, Filipa Marcelo, Francisco Javier Alonso, Ana Arda, Jesús Jiménez-Barbero, Francisco Javier Cañada

{"title":"Reversible Modulation of Glycan Recognition in C-Type Lectins by Calcium/Lanthanide Exchange","authors":"Pablo Valverde, Paola Oquist-Phillips, Ángeles Canales, Ana Diniz, Filipa Marcelo, Francisco Javier Alonso, Ana Arda, Jesús Jiménez-Barbero, Francisco Javier Cañada","doi":"10.1002/cbic.70531","DOIUrl":"https://doi.org/10.1002/cbic.70531","url":null,"abstract":"C-type lectins are Ca2+-dependent glycan-binding proteins involved in immune recognition and host–pathogen interactions. Previous structural studies suggested that lanthanide ions can replace Ca2+ while preserving protein structure, raising the possibility of exploiting paramagnetic lanthanides as NMR probes for studying glycan recognition. Here, we investigated Ca2+/Ln3+ exchange in the immune lectins DC-SIGN and MGL using T2-filtered 19F-NMR binding assays with monofluorinated monosaccharides, together with heteronuclear NMR analysis of 15N-labeled proteins. Chemical shift perturbations, pseudocontact shifts, and paramagnetic relaxation enhancements showed preferential replacement of the Ca2+ ion at the glycan-binding site, while the remaining Ca2+-binding sites were less susceptible to exchange. Unexpectedly, substitution with La3+ or Yb3+ suppresses carbohydrate binding in both lectins, despite preserving the folded structure of the carbohydrate-recognition domains. Glycan recognition was restored upon EDTA-mediated removal of lanthanides in excess Ca2+, demonstrating the reversibility of the process. These findings show that lanthanides do not necessarily behave as functional Ca2+ mimetics in C-type lectins but instead act as reversible disruptors of glycan recognition. Beyond highlighting the need to assess the functional consequences of Ca2+ substitution, this work establishes Ca2+/Ln3+ exchange as a strategy for controlled modulation of lectin activity and for developing new tools to investigate C-type lectin-mediated biological processes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 18","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149007524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Engineered β-Aminopeptidase With Better Product Selectivity for L-Carnosine Production 一种具有较好产品选择性的工程β-氨基肽酶生产l -肌肽。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-14 DOI: 10.1002/cbic.70530

Bi-Han Guan, Wu-Tong Yin, Chen Zhao, Jiang Pan, Jian-He Xu

{"title":"An Engineered β-Aminopeptidase With Better Product Selectivity for L-Carnosine Production","authors":"Bi-Han Guan, Wu-Tong Yin, Chen Zhao, Jiang Pan, Jian-He Xu","doi":"10.1002/cbic.70530","DOIUrl":"10.1002/cbic.70530","url":null,"abstract":"Efficient enzymaticsynthesis of L-carnosine (L-Car) is often limited by competing hydrolysis and side reactions that reduce substrate utilization and product yield. In this study, a β-aminopeptidase (CbAP) from Caulobacter sp. was systematically engineered to enhance catalytic selectivity toward L-Car using β-alaninamide and L-histidine as substrates. Analysis of β-alaninamide-derived byproducts revealed two major competing pathways, namely β-alaninamide hydrolysis and self-ligation into short oligopeptides. To evaluate the balance between L-Car synthesis and competing reactions, a composite apparent selectivity index (RS) was introduced. Structure-guided mutagenesis targeting residues within 4–6 Å of the active site identified several improved variants. Iterative combination of beneficial mutations yielded the optimal mutant CbAPQ138FF96Y (CbAPM2), exhibiting an approximately 2.3-fold increase in RS relative to Q138F and an approximately 3.1-fold increase relative to the wild-type enzyme, with substantial suppression of undesired side reactions. Molecular dynamics simulations indicated that these improvements arise from reduced substrate binding stability and disrupted hydrogen-bonding interactions with β-alaninamide and L-Car. Under optimized 10 mL-scale conditions, CbAPM2 produced 37.3 mM L-Car within 1 h, corresponding to a 74.6% yield based on β-alanine methyl ester, with an STY of 8.44 g L−1 h−1.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962704","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

Isocyanides as a Chemical Tool for Identifying [Fe]-Hydrogenase-Dependent Methanogenesis 异氰酸酯作为鉴定[Fe]-氢酶依赖性甲烷生成的化学工具。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-14 DOI: 10.1002/cbic.70535

Shunsuke Nomura, Seigo Shima

{"title":"Isocyanides as a Chemical Tool for Identifying [Fe]-Hydrogenase-Dependent Methanogenesis","authors":"Shunsuke Nomura, Seigo Shima","doi":"10.1002/cbic.70535","DOIUrl":"10.1002/cbic.70535","url":null,"abstract":"In the hydrogenotrophic methanogens cultivated under nickel-sufficient standard medium (~5 µM Ni2+), two cytosolic [NiFe]-hydrogenases, F420-reducing hydrogenase (Frh) and heterodisulfide reductase (Hdr)-associating hydrogenase (Mvh), mainly provide electrons to the methanogenic pathway. In Methanothermobacter marburgensis under strictly nickel-limited conditions (< 50 nM Ni2+), which are encountered in certain natural environments, Frh and Mvh are strongly downregulated. Under these conditions, a coupled reaction with [Fe]-hydrogenase (Hmd) and F420-dependent methylene-tetrahydromethanopterin dehydrogenase (Mtd) substitutes for the function of Frh, where F420-dependent electron-donating protein (Elp) complexes with Hdr and donates electrons from the reduced form of F420 to Hdr. Thus, Hmd mainly provides electrons to methanogenesis in nickel-limited environments. In this study, to evaluate the potential of isocyanides as an Hmd-specific chemical tool to probe this pathway, we determined their inhibitory effects on the H2-dependent F420-reducing activity in the cell extract and on the in vitro methanogenesis reaction in a cell extract and in a cell suspension. Isocyanides specifically inhibited the activities of the samples from nickel-limited cells. The inhibitory effect on the cell suspension was strengthened by the use of a hydrophobic isocyanide. These results demonstrate their potential as a chemical tool for identifying in situ Hmd-dependent methanogenesis activity in natural environmental samples.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 17","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-Generation Manufacturing: The Evolving Role of Biocatalysis in AstraZeneca 下一代制造：生物催化在阿斯利康的演变作用。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-14 DOI: 10.1002/cbic.70489

Alba Diaz-Rodriguez, Martin A. Hayes, Keith R. Mulholland, Fernando Tur, Samantha Staniland

引用次数: 0