Newsletter 06/2025 edited by Loredano Pollegioni

Do you have news concerning the D-amino acids field to announce? Is there a relevant published paper to mention? Write us and take the advantage of this bimonthly Newsletter.

The Editor’s pick selection of the most intriguing papers is underlined

D-AAs AND PATHOLOGIES:

Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity

Du J-Y, Zhang Z-J, Tan L, Yang J-Y, Yang R-N, Chen Y-L, Tan G-F, Li J, Li W-J, Yang L, Cai J, Shen D-L, Zhu H-R, Fan Z-X, Yuan M-L, Zhang W

mBio. 2025 Nov 12;16(11):e0244725. doi: 10.1128/mbio.02447-25

This study compared gut microbiota and serum metabolites among major depressive disorder (MDD) patients with and without irritable bowel syndrome (IBS), alongside healthy controls, to clarify mechanisms underlying their high comorbidity. Patients with both MDD and IBS showed more severe depression and anxiety, distinct gut microbiota features—including Actinobacteria enrichment—and unique activation of D-amino-acid and glycerolipid metabolic pathways. Serum metabolomics further revealed reduced bile acids and elevated glyceric/glutaconic acids specifically in the comorbid group, linked to bacteria such as Eggerthella lenta and Clostridium scindens. Together, the findings implicate gut microbiota–driven disruptions in bile acid and glyceric acid metabolism in MDD-IBS comorbidity and highlight the gut–brain axis as a potential therapeutic target. This study is registered with the Chinese Clinial Trial Registry as ChiCTR2100041598.

D-serine prevents cognitive impairment in a mouse model of NMDAR encephalitis

Luo H, Han Z, Yang J, Yang X, Li Y, Huang D, Ding R, Cheng L., Ma J, Jiang L

Journal of Neuroimmunology. 2025 409, art. no. 578768, doi: 10.1016/j.jneuroim.2025.578768

This study evaluated whether D-serine can counteract cognitive deficits in a mouse model of anti-NMDAR encephalitis. Mice infused with patient anti-NMDAR antibodies developed memory impairments, reduced hippocampal LTP, loss of synaptic NMDAR clusters, and suppressed CaMKII/ERK/CREB signaling. Daily D-Ser treatment significantly improved cognition and LTP and restored downstream NMDAR signaling, despite only modest effects on NMDAR clustering. These findings suggest that D-Ser may serve as a useful adjunct to immunotherapy by rescuing NMDAR-dependent signaling and cognitive function.

Detection and functional assessment of D-amino acids as potential biomarkers in neurological disorders

Talebi M, Sharifi-Ardani SE, Ghannadzadeh FS, Sattarpour M, Jahanseir A, Hashemi S, Jahani R

Mol Biol Rep. 2025 Nov 7;53(1):60. doi: 10.1007/s11033-025-11207-6

This review examines the diverse roles of D-amino acids (D-AAs) in neurological disorders and highlights their potential as diagnostic biomarkers. Specific D-AAs—including D-serine, D-alanine, D-glutamate, and D-aspartate—are discussed in the context of neurodegenerative, psychiatric, cerebrovascular, and epileptic conditions, especially through their influence on NMDA receptor signaling. The article also surveys current analytical methods used to detect D-AAs in biological samples. Looking ahead, improved detection technologies and machine-learning–enhanced metabolomics may enable more precise disease profiling and therapeutic innovation.

Metagenomic analysis of the gut microbiota in major depressive disorder with different antidepressant efficacy: A prospective cohort study

Du JY, Qin FL, Yang RN, Chen YL, Tan GF, Li WJ, Yang L, Cai J, Shen DL, Zhu HR, Yuan ML, Zhang W

J Affect Disord. 2025 Nov 13;394(Pt B):120709. doi: 10.1016/j.jad.2025.120709

This study compared baseline gut microbiota in major depressive disorder (MDD) patients who later responded or did not respond to Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) treatment. While clinical and demographic factors were similar, responders and non-responders showed distinct microbial compositions and metabolic pathways. Non-responders had higher levels of certain Bacteroides species and enrichment of steroid biosynthesis pathways, whereas responders showed higher levels of Hungatella and enrichment of D-amino acid metabolism pathways. These findings suggest that gut microbiota may help predict antidepressant response and guide future therapeutic strategies, though validation in larger cohorts is needed.

D-Alanine Hydrochloride and D-Alanine Dipeptide Have Biological Activity and Promote Human Proximal Tubular Epithelial Cell Viability

Sako K, Saito Y, Nakade Y, Linh HT, Koshino A, Horikoshi K, Yuasa T, Tamai A, Tsuge S, Minami T, Oshima M, Nishioka R, Ito K, Mizushima I, Hara A, Sakai N, Shimizu M, Mita M, Wada T, Nakagawa-Goto K, Iwata Y

Chem Biodivers. 2025 Nov 5:e01108. doi: 10.1002/cbdv.202501108

This study explored D-alanine derivatives as potential treatments for acute kidney injury (AKI) without the need for L-alanine stabilization. In HK-2 tubular epithelial cells, both D-alanine hydrochloride and a D-alanine dipeptide improved cell viability, with D-alanine hydrochloride showing the strongest protection under hypoxic stress. These compounds also promoted cell cycle progression and increased cyclin B1 expression. Although based on in vitro data, the findings indicate that stabilized synthetic D-alanine molecules may serve as promising AKI therapeutic candidates.

The role of DAAO in cognitive impairment of offspring mice induced by arsenic exposure during early developmental stage

Niu Z, Xie X, Jin X, Yu H, Jin G, Wang Y

PLoS One. 2025 Sep 29;20(9):e0333414. doi: 10.1371/journal.pone.0333414

This study examined how D-amino acid oxidase (DAAO) contributes to arsenic-induced cognitive impairment in offspring mice. Developmental arsenic exposure reduced hippocampal D-serine, L-serine, serine racemase, NMDAR, and synaptic protein levels while increasing DAAO expression. Inhibiting DAAO with CBIO partially restored D-serine and NMDAR levels. The findings suggest that altered D-serine metabolism via elevated DAAO activity plays a key role in arsenic-related cognitive deficits during early development.

Impact of D-Amino Acids in Schizophrenia

Dursun SM, Dursun LH, Baker GB

Biomolecules. 2025 Sep 2;15(9):1270. doi: 10.3390/biom15091270

This review highlights growing evidence that several D-amino acids—especially D-serine, D-aspartate, and D-alanine—play important roles in glutamatergic signaling and may contribute to the etiology of schizophrenia. These D-AAs modulate NMDA receptors and can influence additional pathways such as mGlu5 activation and presynaptic glutamate release. Both preclinical and clinical studies suggest that reduced levels of these D-AAs, or disruptions in their metabolic enzymes, are associated with schizophrenia-related behaviors and patient biomarker profiles. The review also discusses emerging interest in D-cysteine and considers therapeutic strategies targeting D-AAs or their metabolism, as well as key challenges for future research.

D-AAs AND PHYSIOLOGICAL ROLE:

Mechanistic Insights into D-Alanine-Induced Plant Growth Inhibition: Synergistic Roles of Transport, Transcriptional Regulation, and Metabolic Perturbations

Chen H, Zhang Y, Shi Y, Zeng S, Chen K, Mou W, Li D

J Agric Food Chem. 2025 Oct 29;73(43):27338-27350. doi: 10.1021/acs.jafc.5c08562

This study uncovers how D-alanine (D-Ala) inhibits growth in the liverwort Marchantia polymorpha. The authors show that D-Ala is taken up by the transporter MpLHT1 and partially metabolized by MpDAT, while the transcription factor MpBZIP4 negatively regulates D-Ala tolerance. The flavonoid luteolin further exacerbates D-Ala toxicity, likely through inhibition of carbonic anhydrase, and expression of Arabidopsis AtACO4 intensifies these effects by disrupting luteolin metabolism and carbonic anhydrase gene expression. Together, the findings reveal a multilayered mechanism—combining transport, transcriptional responses, and metabolic disturbances—that explains D-Ala–induced growth suppression in plants.

D-AAs AND CHIRALITY:

Comprehensive Characterization of D,L-Valine: Molecular Structure, Vibrational Analysis, Biological Implication and Molecular Dynamics Simulation

Garima K, Kumar M, Ahmad S, Khatoon K, Savita S, Ali A, Arora H, Aljohani M, Singh R, Siddiqui N, Alvi S, Javed S, Srivastav SK

J Computat Biophys Chem. 2026 25 (9), 1351 – 1373, doi: 10.1142/S2737416525500966

This study provides a comprehensive computational and experimental characterization of D,L-valine, validating structural parameters and vibrational spectra against experimental data. Electronic analyses reveal its charge distribution, reactive sites, and non-covalent interaction patterns. Additional evaluations further clarify its stability and intermolecular behavior. Molecular docking and ADME assessments suggest potential biological relevance, offering insights into D,L-valine’s possible applications in pharmaceutical and biochemical research.

Chirality recognition of amino acid by combining machine learning method and sliding window technique

Guo S, Li J, Jiang W, Yang J, Du Y, Luo T, Anwar A, Qi L

Optics and Laser Technology. 2025 192, art. no. 113937. doi: 10.1016/j.optlastec.2025.113937

This study demonstrates that combining infrared spectroscopy with machine learning (ML) enables accurate discrimination of L- and D-enantiomers of alanine, cysteine, and glutamine. By applying three ML models along with a sliding-window spectral analysis, the authors show that chiral recognition performance depends strongly on the selected spectral region and window parameters. The approach overcomes the complexity of traditional IR analysis and achieves precise enantiomer identification. These findings expand the potential of IR-based, ML-assisted chirality sensing for applications in analytical chemistry, biomedicine, and pharmaceutical research.

ENZYMES ACTIVE ON D-AAs:

Site-specifically immobilized D-amino acid dehydrogenase for the synthesis of D-phenylalanine

Boros K, Iszlai AE, Barabás LE, Bencze LC, Toşa MI

N Biotechnol. 2025 Sep 30;90:145-154. doi: 10.1016/j.nbt.2025.09.006

This work advances the biocatalytic production of aromatic D-amino acids by developing site-specifically immobilized variants of a Ureibacillus thermosphaericus D-amino acid dehydrogenase (UtDAADH). By mutating surface serine residues to cysteine, the enzyme was covalently immobilized on maleimide-functionalized Purolite® supports, with Cys2 and Cys192 variants showing more than double the activity of non-specific immobilization. The best-performing catalyst, immobilized via Cys2, retained strong activity over 10 reuse cycles and enabled efficient, scalable synthesis of enantiopure D-phenylalanine with high yields. These results highlight the utility of site-specific immobilization for improving DAADH robustness and industrial applicability.

D-AAs AND BIOTECHNOLOGY:

Valuable Compounds from Pollutants: Converting PET into Enantiopure Alanine

Rosini E, Battaglia C., Miani D, Molinari F, Arrigoni F, Piarulli U, Molla G, Pollegioni L

ACS Catal. 2025, 15, 21, 17829–17843. doi:10.1021/acscatal.5c06530

This study develops a tandem enzymatic–microbial system that depolymerizes post-consumer PET and converts it into enantiopure D- or L-alanine. An engineered PET-degrading enzyme (S101N/F243T-ΔLCC) active at 37 °C first breaks PET into terephthalic acid (TPA) and ethylene glycol, after which recombinant E. coli strains transform TPA into 2-pyrone-4,6-dicarboxylic acid and then into pyruvate. A final enzymatic amination step yields optically pure alanine. Using 12 enzymes from four organisms, the process achieved 50 mg alanine from 170 mg PET, demonstrating the feasibility of upcycling plastic waste into valuable biomolecules through a sustainable biocatalytic pathway.

Hybrid nanoflower-incorporated foldable paper biosensor for colorimetric detection of sodium benzoate based on inhibition of D-amino acid oxidase

Dang TV, Kim KM. Nguyen QH, Kim MI

Microchemical Journal. 2025 219, art. no. 115979. doi: 10.1016/j.microc.2025.115979

This study introduces a foldable paper-based microfluidic biosensor for rapid, portable, and sensitive detection of sodium benzoate (SB). The device exploits SB’s ability to inhibit D-amino acid oxidase, thereby reducing D-serine oxidation and subsequent H₂O₂ production, which is read out through a colorimetric HRP–Cu nanoflower peroxidase reaction. The dual-pH, two-step design enables a clear blue color decrease proportional to SB concentration, achieving a low detection limit of 2.3 μM and accurate measurements in real food samples. This foldable, low-cost platform provides a generalizable approach for on-site food safety monitoring and point-of-care biosensing.

An enzymatic cascade enables sensitive and specific proximity labeling proteomics in challenging biological systems

Sroka TJ, Sanwald LK, Prasai A, Hoeren J, Trivigno V, Chaumet V, Krauß LM, Weber D, Yildiz D, von der Malsburg K, Walentek P, Haberkant P, Schrul B, Feistel K, Mick DU

Nat Commun. 2025 Nov 3;16(1):9691. doi: 10.1038/s41467-025-65405-8

This work introduces an improved proximity-labeling strategy, iAPEX, which pairs APEX2 with a D-amino acid oxidase to generate hydrogen peroxide locally, thereby reducing toxicity and non-specific background. Using iAPEX, the authors successfully profile the proteome of the primary cilium in cell lines that are difficult to study with conventional APEX methods and uncover previously unrecognized ciliary proteins. The approach also works across multiple cellular compartments and in Xenopus laevis, demonstrating its versatility and potential for future in vivo applications.

D-AAs IN BACTERIA:

A Lyt at the end of the tunnel? Unraveling the complex interactions of the N-acetylglucosaminidase LytG in cell wall metabolism

Hernandez J, Duval J, Rauff T, Hall E, Gallati M, Haubrich BA, Thoma M, Aponte E, Basu A, DeGiorgis JA, Reid CW

RSC Chem Biol. 2025 Sep 30. doi: 10.1039/d5cb00151j

This study uses the small-molecule inhibitor masarimycin to reveal the biological role of the peptidoglycan-degrading enzyme LytG in Bacillus subtilis. Chemical inhibition of LytG—unlike genetic deletion—disrupted cell elongation, division-plane placement, and cell wall homeostasis, triggering stress responses and producing asymmetrical wall thickening. Synergy analyses linked LytG activity to late-stage peptidoglycan cross-linking and to enzymes such as DacA and D,D-endopeptidases. Overall, the work shows how chemical probes can uncover autolysin functions critical for bacterial growth and division.

D-AAs IN PEPTIDES AND PROTEINS:

HighFold-MeD: a Rosetta distillation model to accelerate structure prediction of cyclic peptides with backbone N-methylation and D-amino acids

Cao Z, Cao S, Wang L, Wang Z, Mao Q, Guo J, Duan H

J Cheminform. 2025 Nov 10;17(1):167. doi: 10.1186/s13321-025-01111-3

This work introduces HighFold-MeD, a deep learning framework designed to rapidly and accurately predict structures of cyclic peptides containing backbone N-methylated and D-amino acids. By generating a large Rosetta SCP–based dataset and fine-tuning AlphaFold with expanded amino acid representations and a cyclic-specific positional matrix, the model effectively distills Rosetta’s structural knowledge. HighFold-MeD matches Rosetta’s accuracy while achieving a 50-fold speedup, further improved by a force-field refinement step. This accelerated approach enables large-scale structural modeling to support cyclic peptide drug discovery.

Spatially Mapping Neuropeptide Isomers via MALDI Trapped Ion Mobility MS Imaging

Okyem S, Trinklein TJ, Rubakhin SS, Sweedler JV

Anal Chem. 2025 Oct 28;97(42):23370-23380. doi: 10.1021/acs.analchem.5c04297

This study demonstrates that MALDI-TIMS-MSI can image neuropeptide stereoisomers directly in tissue with single-cell resolution. Applying the method to the Aplysia CNS, the authors mapped both L- and D-amino-acid–containing peptide forms and found that DAACPs are abundant in neuropil but absent from neuronal somata. Tandem MS validation confirmed 13 resolved stereoisomers from six neuropeptides. The work establishes a powerful approach for spatially characterizing peptide isomerization and its role in neuropeptide regulation.

Targeted Modification of the Antimicrobial Peptide DGL13K Reveals a Naturally Optimized Sequence for Topical Applications

Gorr SU

Microorganisms. 2025 Oct 14;13(10):2355. doi: 10.3390/microorganisms13102355

This paper evaluates strategies to improve DGL13K, a fully D-amino-acid antimicrobial peptide known for its stability, broad-spectrum activity, and low risk of inducing resistance. Various sequence modifications—including amino acid substitutions, stereochemical changes, and N-terminal PEG or myristoyl additions—were tested to enhance potency and reduce toxicity, but none outperformed the original peptide. Although some variants showed altered specificity or reduced hemolysis, all peptides, including DGL13K, exhibited reduced activity in 50% serum, limiting systemic use. Overall, the work suggests that DGL13K is already highly optimized and remains a strong candidate for topical or localized antimicrobial therapies.

Rational design of thrombin-derived VFR12 analogs with enhanced antimicrobial, antibiofilm, and anti-inflammatory properties

Jahan I, Kumar SD, Ajish C, Lee CW, Shin SY, Yang S

Sci Rep. 2025 Nov 19;15(1):40876. doi: 10.1038/s41598-025-24789-9

This study optimized the thrombin-derived peptide VFR12 through targeted amino acid and stereochemical modifications to create potent, safe, and stable antimicrobial candidates. Several engineered 12-mer analogs showed strong broad-spectrum activity, excellent biocompatibility, robust antibiofilm effects, and notable anti-inflammatory properties. D-amino-acid variants were especially stable and effective, with VFR12-a8(L)-d emerging as the lead candidate. Overall, the work provides a framework for next-generation host-defense peptides that address antibiotic resistance and sepsis through multiple therapeutic mechanisms.

Peptide-based ligand antagonists block a Vibrio cholerae adhesin

Wang M, Du G, Yongo-Luwawa C, Lu A, Kinrade B, Munro K, Klose KE, Lubell WD, Davies P, Guo S

FEBS Lett. 2025 Nov 20. doi: 10.1002/1873-3468.70231

Vibrio cholerae uses the adhesin FrhA to attach to host tissues, making this interaction a promising target for anti-adhesion therapeutics. This study identifies a minimal D-amino-acid tripeptide with greatly improved affinity and predicted stability compared to the previously known AGYTD pentapeptide. Structural analysis reveals how FrhA recognizes peptide ligands and guides the design of potent adhesion blockers. These findings offer a blueprint for developing next-generation treatments that prevent cholera infection without driving antibiotic resistance.

Cryo-EM Structures Reveal Nonmirror-Image Binding of L- and D-Peptide Enantiomers at α7 Nicotinic Acetylcholine Receptor

Xu Z, Cao X, Liu T, Chen H, Liu S, Tian C, Sun D

Chembiochem. 2025 Nov 8;26(21):e202500599. doi: 10.1002/cbic.202500599

This study reports cryo-EM structures of the α7 nicotinic acetylcholine receptor bound to the L-peptide LKP1794 and its D-enantiomer DKP1794, offering the first molecular view of how D-peptides engage this receptor. Both peptides bind at the orthosteric site, but the D-peptide does not simply adopt a mirror-image pose; instead, it uses a hybrid binding mode involving partial mirror symmetry and a flipped backbone orientation. These findings reveal a distinct recognition mechanism that differs from the traditional retro-inversion model. The work provides key structural insights to guide the design of stable, high-affinity D-peptide modulators of α7-nAChR.

e3MPH16: A D-Glutamic Acid-Substituted Peptide for Efficient and Low-Cytotoxicity Cytosolic Delivery of Macromolecules

Kawaguchi Y, Kiyokawa M, Furuyama Y, Futaki S

Chem Pharm Bull (Tokyo). 2025;73(9):907-913. doi: 10.1248/cpb.c25-00478

This study enhances a previously developed cytosolic delivery peptide by introducing D-amino-acid substitutions to improve stability and intracellular transport efficiency. The modified peptide, e3MPH16, which includes D-glutamic acid residues at the N-terminus, shows improved resistance to serum proteases and markedly increases the delivery of functional macromolecules—including Cre recombinase and full-length antibodies—compared with the parent peptide E3MPH16. Importantly, these gains are achieved without elevating membrane lysis or cytotoxicity. The findings highlight D-amino-acid–substituted peptides as a promising strategy for enabling intracellular delivery of unmodified antibodies.

Influence of chirality in supramolecular self-assembly of α/β-hybrid dipeptides

Sarkar A, Shill S, Roy S, Mandal B

Journal of Molecular Structure. 2026 1352, art. no. 144545. doi: 10.1016/j.molstruc.2025.144545

This study examines how chirality and backbone structure influence the self-assembly of three Fmoc-protected dipeptides containing anthranilic acid. All three peptides form β-sheet structures in the crystalline state, but substituting the central chiral residue leads to distinct supramolecular morphologies. In methanol–water, the L-Ala, D-Ala, and Gly variants self-assemble into tape-like, fibrous, and rod-like nanostructures, respectively. The findings demonstrate that subtle stereochemical and conformational differences strongly shape peptide self-assembly behavior.

D-AAs AND ANALYTICAL METHODS (AND FOODS):

The distribution of D-amino acid in food and drug and their effects on mouse metabolism

Zhang Y, Li X, Li Z, Zhang P, Yang D, Zeng C, Xiao W, Zhao Y, Chen X, Yang G, Deng Z

J Pharm Biomed Anal. 2026 Jan 15;268:117186. doi: 10.1016/j.jpba.2025.117186

This study surveyed D-amino acids (D-AAs) in foods and pharmaceuticals and examined their metabolic effects in mice. D-AAs were found in all tested products, with D-aspartic acid, D-histidine, and D-leucine most abundant. In a 20-day feeding study, several D-AAs accumulated dose-dependently in mouse tissues and serum, and metabolomic profiling revealed major alterations—especially in lipid and lipid-like metabolites. Disrupted glycerophospholipid and choline metabolism suggests that dietary D-AAs can significantly affect lipid homeostasis, neurotransmission, and immune regulation.

Chiral amino acids fingerprinting analysis based on gold nanoparticles sensing array and its application in alcoholic beverages identification

Liu Q, Shi H, Feng Y, Xu J, Liu C, Zhao X, Zou H, Wang J

Food Chemistry. 2025 496, art. no. 146665. doi: 10.1016/j.foodchem.2025.146665

This study introduces a gold nanoparticle–based sensing array capable of enantioselectively recognizing 12 amino acids and their enantiomeric excess. Using three AuNP variants, the platform produces distinct chiral “fingerprints” that, when analyzed with LDA and HCA, achieve 100% accuracy in classifying red wines, Baijiu types, and blind samples. A partial least squares regression model also accurately quantified Baijiu adulteration levels. The method provides a fast, non-destructive tool for chiral amino acid analysis, offering strong potential for quality control and authenticity verification in the alcoholic beverage industry.

Development and validation of a sensitive assay for analysis of D/L-serine in cells using ultra-high performance liquid chromatography-fluorescence detector

Liu L, Ren S, Hao Y, Yue L, Yue C, Li L, Zhang W, Gao Z, Hai X

Talanta. 2026 297, art. no. 128634. doi: 10.1016/j.talanta.2025.128634

This study establishes a robust UPLC–fluorescence detection method for accurately quantifying D- and L-serine in cells. Following OPA/NAC derivatization, the enantiomers were cleanly separated on a C18 column and detected with high sensitivity, achieving clear baseline resolution and a quantitation limit of 0.1 nmol/mL. The method showed strong accuracy and precision and was successfully applied to measure D/L-serine levels across different cell lines. Overall, it provides a simple and reliable analytical tool for investigating cellular serine metabolism and related biological mechanisms.

Inner filter effect regulated upconversion sensing platform for non-invasive detection of two gastric cancer relevant substances

Cheng G, Shao X, Lin P, Zhang J, Lu L

Biosens Bioelectron. 2025 Sep 25;291:118029. doi: 10.1016/j.bios.2025.118029

This study presents a dual-mode sensing platform capable of simultaneously detecting two gastric cancer–related biomarkers—D-amino acids (D-Pro and D-Ala) and urease—in a single assay. Using multi-peak emission UCNPs assembled via an emulsion strategy and polyethylenimine (PEI)-modified Cu-based Prussian blue analog nanozymes, the system achieves sensitive colorimetric and luminescent detection through an IFE-based signal modulation mechanism. Sodium dodecyl sulfate further enhances nanozyme catalytic activity, boosting sensitivity. The platform reaches detection limits relevant to early gastric cancer screening, offering a promising noninvasive diagnostic approach.

Chiral Discrimination of all Proteinogenic Amino Acid Enantiomers by Nanopore Sensing

Zhang H, Wang K, Zhou X, Wang Y, Zhang P, Li W, Huang S

Angew Chem Int Ed Engl. 2025 Oct 21:e202515531. doi: 10.1002/anie.202515531

This study presents a nickel-ion chelated hetero-octameric Mycobacterium smegmatis porin A (MspA) (MspA-NTA-Ni) nanopore sensor capable of directly identifying all 19 D-amino acids alongside their L-enantiomers at the single-molecule level. Coupled with supervised machine learning, the platform achieves ~99% accuracy in distinguishing amino acid enantiomers and successfully profiles D/L compositions in hydrolyzed D-peptide samples. Overall, it enables simultaneous sensing of all 39 amino acid enantiomers with high accuracy, offering a powerful tool for analyzing mixed D,L-amino acid samples and advancing nanopore-based sequencing of D-peptides and D-proteins.

Nano-molecular dual-dimensional collaborative sensor for chiral amino acid discrimination and mechanism insights

Yang X, Li S, Zhao P, Li X, Zhang G, Zhang Z, Han P, Zhao Y, Zhang T, Liu F, Zhang C, Zhang Y, Wang H

Biosens Bioelectron. 2026 Jan 15;292:118093. doi: 10.1016/j.bios.2025.118093

In this study a dual-dimensional chiral recognition biosensor was developed by integrating Fe-N co-doped L/D chiral carbon nanotubes with L/D-histidine–modified ZIF-8. The combined system shows strong synergistic effects, enabling highly sensitive and selective discrimination of Trp, Tyr, and Cys enantiomers, with nanomolar detection limits and clear chiral response ratios. Density functional theory analysis further clarifies the molecular basis of the sensor’s enantioselectivity. The platform demonstrates strong performance in real-sample testing and offers a foundation for next-generation chiral biosensors relevant to drug screening, diagnostics, and life science research.

Chromatographic isolation for performing enantiomer-specific radiocarbon analysis (ESRA): first method development for individual L- and D-amino acids

Blattmann TM, Sun Y, Ogawa NO, Takano Y, Haghipour N, Ishikawa NF, Eglinton TI, Ohkouchi N

Progress in Earth and Planetary. Science 2025 12 (1), art. no. 84. doi: 10.1186/s40645-025-00764-w

This work presents the first method for enantiomer-specific radiocarbon analysis of underivatized L- and D-amino acids. Using a two-dimensional preparative HPLC workflow, alanine and valine enantiomers were cleanly separated and further purified on a mixed-mode reversed-phase cation-exchange column. The isolated enantiomers were then successfully analyzed for radiocarbon content using EA-AMS, with baseline separation and low analytical blanks. This approach enables radiocarbon measurements of individual amino-acid enantiomers without derivatization, opening new possibilities for biochemical and geochemical applications.

INFORMATION

The D-amino acids International Research Center “DAAIR“ has been established in Gerenzano (Varese, Italy) in 2019 with the aim to support and perform scientific research projects and activities on the field of D-amino acids. The Center, located inside the Fondazione Istituto Insubrico Ricerca per la Vita, is aimed to represent a pole of excellence at international level for dissemination and research involving the D-amino acids (Director Silvia Sacchi).

Info@d-aminoacids.com

director@d-aminoacids.com

D-AMINO ACIDS INTERNATIONAL RESEARCH CENTER

INFO@D-AMINOACIDS.COM