D-AAS AND PHYSIOLOGICAL ROLES:
D-Valine as a mirror-image antifibrotic agent: Inhibiting fibroblast proliferation and attenuating airway fibrosis
Ekici MA, Uluşan A, Şanlı M, Kahraman D, Bağcı Özyaşar C, Işık AF
Turk Gogus Kalp Damar Cerrahisi Derg. 2026. doi: 10.4274/tjtcs.2026.28842
This study identifies D-valine as a promising antifibrotic D-amino acid capable of reducing fibroblast proliferation and attenuating fibrosis in experimental tracheal stenosis. By interfering with valine-dependent protein synthesis, D-Valine reduced submucosal thickening and extracellular matrix deposition in vivo, suggesting potential applications for the treatment of airway fibrotic disorders.
A novel mechanism of exercise-induced cognitive protection in ageing: D-amino acid oxidase /D-serine-dependent modulation of NMDAR signalling
Tong X, Yang Y, Liu Z, Luo R, Chen F, Liu Y, Wang Z, Tao X, Liu W
Ageing Res Rev. 2026; 119:103179. doi: 10.1016/j.arr.2026.103179
This review highlights the therapeutic potential of the D-amino acid oxidase/D-serine/NMDAR axis in age- related cognitive decline. Exercise may preserve central D-serine homeostasis by modulating DAAO activity, thereby enhancing NMDAR signaling and activating CaMKII–CREB–BDNF pathways involved in synaptic plasticity and memory. These findings identify D-amino acid metabolism as a promising target for non-pharmacological interventions against cognitive aging.
Clonal Stabilization Reveals a DAO/3MST-Expressing MDCK Subpopulation With Robust D-Cysteine-Mediated H S Production
Miyamoto A, Ueno H, Kimura H, Nakagawa T, Shibuya N
FASEB Journal, 2026, 40 (6), art. no. e71699. doi: 10.1096/fj.202503702RR
This study demonstrates that renal epithelial cells produce hydrogen sulfide (H2S) through a D-cysteine-dependent pathway involving D-amino acid oxidase and 3-mercaptopyruvate sulfurtransferase. The findings identify epithelial cell subpopulations capable of efficient D-cysteine metabolism and suggest that D-amino acid-derived H2S production plays a protective role in kidney physiology and ischemia–reperfusion injury.
D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease
Wang J, Guo Y, Han W, Zhang H, Jiang P
Cellular and Molecular Neurobiology, 2026, 46 (1), art. no. 65. doi: 10.1007/s10571-026-01696-9
This review highlights D-serine as a central regulator of brain and systemic physiology beyond its classical role as an NMDA receptor co-agonist. D-serine is implicated in synaptic plasticity, metabolism, epigenetic regulation, and peripheral organ function, while disrupted D-serine homeostasis contributes to disorders including Schizophrenia, Alzheimer’s disease, neuropathic pain, and diabetic complications. Emerging therapies targeting serine racemase and D-amino acid oxidase pathways may enable personalized approaches in neurology and psychiatry.
D-AAs AND PATHOLOGIES:
D-amino acids restrain macrophage IL-1β release through gasdermin D acetylation
Wu Z, Hu Q, Shen Y, Fu J, Liu B, Zhang M, Hung I, Liu C, Ren W
Sci Adv. 2026; 12(18):eaed1676. doi: 10.1126/sciadv.aed1676
This study reveals an unexpected immunoregulatory role of D-amino acids in macrophage-mediated inflammation. Inhibition of D-amino acid oxidase and D-aspartate oxidase increases intracellular D-amino acid levels, suppressing IL-1β release through GSDMD acetylation. By enhancing pyruvate dehydrogenase activity and acetyl-CoA production, D-amino acids attenuated inflammatory responses and protected against sepsis in vivo, highlighting their therapeutic potential in inflammatory diseases.
Advances in schizophrenia research and treatment: exploring neurotransmitter imbalances, genetics, and innovative therapies
Škutová K, Fišar Z, Hroudová J
Prog Neuropsychopharmacol Biol Psychiatry. 2026, 19:111749. doi:10.1016/j.pnpbp.2026.111749
Schizophrenia is a severe neurodevelopmental disorder driven by genetic susceptibility, neurotransmitter imbalance, neuroinflammation, oxidative stress, and gut-brain axis dysfunction. Current antipsychotics often show limited efficacy on negative and cognitive symptoms and can cause major side effects. Novel therapeutic strategies target glutamatergic, serotonergic, muscarinic, GABAergic, and D-amino acid pathways, including D- amino acid oxidase inhibitors. Recently approved drugs and compounds in advanced clinical trials aim to improve overall symptom control, cognition, and treatment tolerability.
Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder
Maffioli E, Errico F, Motta Z, di Vito R, Grana J, De Grandis E, Boeri S, Bruno C, Riccio MP, Iasevoli F, Di Maio M, Nuzzo T, Bravaccio C, Bagnasco S, Gelzo M, Castaldo G, de Bartolomeis A, Negri A, Pollegioni L, Tedeschi G, Usiello A
Schizophrenia (Heidelb). 2026. doi: 10.1038/s41537-026-00758-7
This multicenter study identifies disorder-specific alterations in D-amino acid metabolism in schizophrenia and autism spectrum disorder. Changes in serum levels of serine racemase, D-amino acid oxidase, D-aspartate oxidase, and pLG72 were associated with altered D-serine and D-aspartate metabolism, supporting the role of NMDA receptor dysregulation in neuropsychiatric disorders. These findings highlight D-amino acid-related enzymes as promising biomarkers and potential therapeutic targets.
Rescue of astrocytic ASCT1 expression and D-serine uptake attenuates remifentanil-induced hyperalgesia
Chen C, Shi Y, Wan Y, Zhu Z, Feng Y, Song M, Li X, Shi J
Biochem Biophys Res Commun. 2026; 824:153944. doi: 10.1016/j.bbrc.2026.153944
This study identifies an astrocytic ASCT1–D-serine pathway as a key regulator of remifentanil-induced hyperalgesia. Remifentanil increases spinal D-serine levels and reduces astrocytic ASCT1 expression, enhancing NMDA receptor-dependent sensitization and pain hypersensitivity. Modulating D-serine metabolism through D-amino acid oxidase or restoring ASCT1 function significantly attenuated hyperalgesia, highlighting D-amino acid signaling as a promising therapeutic target for opioid-induced pain sensitization.
Microglial serine racemase knockout alleviates Alzheimer-like neuropathology and behavioral deficit via lactylation-mediated anti-inflammation
Zhou J, Yang Y, Liu S, Chen J, Liao H, Liang W, Zhang Z, Wang Y, Liu Y, Zhang H, Jiang H, Lin W, Qu J, Barger SW, Wu S
Communications Biology, 2026, 9 (1), art. no. 493. doi: 10.1038/s42003-026-09772-y
This study identifies microglial serine racemase (SR) as a key regulator of neuroinflammation and amyloid pathology in Alzheimer’s disease. Deletion of SR enhanced microglial phagocytosis, promoted anti-inflammatory signaling through histone lactylation, reduced amyloid plaque burden, and improved cognitive performance in AD mouse models. The findings highlight D-serine metabolism and its interaction with D-amino acid oxidase as promising therapeutic targets in AD.
Conjecture for a free radical epimerization process in Alzheimer, Parkinson, Lewy body, amyotrophic lateral sclerosis, progressive Supranuclear Palsy and Creutzfeldt Jakob diseases
Deloncle R
Experimental Neurology, 2026, 403, art. no. 115812 doi: 10.1016/j.expneurol.2026.115812
This review proposes that free radical-induced epimerization of L-amino acids into D-amino acid-containing proteins may contribute to the formation of protease-resistant aggregates in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Creutzfeldt-Jakob disease. Altered copper homeostasis and oxidative stress may promote protein misfolding, suggesting that restoration of brain copper balance could represent a therapeutic strategy against neurodegeneration.
A phase 2 Chirality in hydrogels assembled from D- or L-amino acid derivatives regulates immunological responses during diabetic wound healing
Zhao Y, Li Z, Song S, Liu G, Li T, Zhong W, Liu Y, Chen Y, Wang H, Zhang J, Yuan W, Yang J, Cheng Y, Zhu X, Ren X, Liu H, Zhao Y
Journal of Controlled Release, 2026, 394, art. no. 114891. doi: 10.1016/j.jconrel.2026.114891
This study demonstrates that supramolecular hydrogels incorporating D- or L-amino acid derivatives can modulate immune responses through matrix chirality. Right-handed chiral extracellular matrices promoted macrophage polarization toward a reparative M2 phenotype, enhanced PI3K-Akt signaling, and improved healing in Diabetic ulcer models. These findings highlight the potential of D-amino acid-based biomaterials for immunomodulatory regenerative medicine and advanced wound therapies.
A randomized controlled trial of luvadaxistat in treatment of adults with cognitive impairment associated with schizophrenia: results from the ERUDITE study
Khin NA, Fan RH, Ge T, Klein HS, Ballon JS, Brar S, Harvey PD, Kantrowitz JT, Keefe RSE, Asgharnejad M, Murthy V, Roberts E, Singh JB
Neuropsychopharmacology. 2026. doi: 10.1038/s41386-026-02410-5
The phase 2 ERUDITE study evaluated luvadaxistat, a selective D-amino acid oxidase inhibitor, as a treatment for cognitive impairment in schizophrenia. Although the drug showed a favorable safety and tolerability profile, it did not significantly improve cognitive performance compared with placebo. These findings highlight both the clinical relevance and the complexity of targeting D-amino acid metabolism and NMDA receptor modulation in schizophrenia.
Gender-specific effects of sodium benzoate on cognitive improvement in individuals with dementia: a meta-analysis of randomized controlled trials
Yeh PY, Liao RM, Chang HY, Lin WT, Chen YZ, Lane HY, Lin CH
Eur Arch Psychiatry Clin Neurosci. 2026. doi: 10.1007/s00406-026-02223-z
This meta-analysis shows that sodium benzoate, an inhibitor of D-amino acid oxidase, significantly improves cognitive performance in patients with mild cognitive impairment and dementia, likely by enhancing D-serine availability and NMDA receptor signaling. Cognitive benefits were particularly evident in female patients, supporting the therapeutic potential of D-amino acid modulation in neurodegenerative disorders.
ENZYMES ACTIVE ON D-AAs:
Enhanced Thermal Stabilization of Yeast D-Aspartate Oxidase Through Intersubunit Disulfide Bond Engineering
Zaitsu S, Imanishi D, Ogata N, Takahashi S
Biotechnol Appl Biochem. 2026. doi: 10.1002/bab.70163
This study describes the engineering of the flavoenzyme D-aspartate oxidase from Cryptococcus humicola to improve its thermal and operational stability for biotechnological applications. Introduction of an intersubunit disulfide bond significantly enhanced resistance to heat-induced inactivation without affecting catalytic efficiency toward D-aspartate, supporting the development of more robust D-amino acid biosensors and biocatalytic platforms.
Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning
Vanella R, Boult S, Küng C, Nash MA
Nature Communications, 2026, 17 (1), art. no. 3245. doi: 10.1038/s41467-026-69913-z
This study applies enzyme proximity sequencing (EP-Seq) to map how mutations alter substrate specificity in D-amino acid oxidase from Rhodotorula gracilis. Analysis of thousands of variants identified both active-site and allosteric mutations capable of dramatically reshaping D-amino acid selectivity, including variants with up to 230-fold substrate preference changes. These findings provide a powerful framework for AI-guided engineering of highly selective biocatalysts.
Biocatalytic potential of Ensifer adhaerens S-5 D-Carbamoylase: Insights from in silico and in vitro analyses
Paronyan M, Koloyan H, Aganyants H, Avetisyan S, Melkumyan M, Soghomonyan T, Khoyetsyan L, Hambardzumyan A, Sakanyan V, Hovsepyan A
Journal of Genetic Engineering and Biotechnology, 2026, 24 (2), art. no. 100676. doi: 10.1016/j.jgeb.2026.100676
This study characterizes a D-carbamoylase from Ensifer adhaerens as a promising biocatalyst for sustainable D- amino acid production. Combining in silico modeling, molecular dynamics, and biochemical analyses, the enzyme showed activity toward several N-carbamoyl-D-amino acids relevant to the hydantoinase process. These findings support the development of greener enzymatic platforms for industrial synthesis of pharmaceutical and biotechnological D-amino acid derivatives.
D-AAs AND BIOTECHNOLOGY:
Dose-dependent mitochondrial H2O2 signaling drives toxicity or stress adaptation and longevity in fission yeast
de Cubas L, Crevatin MF, Vega M, Boronat S, Ayté J, Hidalgo E
Cell Rep. 2026; 45(4):117277. doi: 10.1016/j.celrep.2026.117277
One-Pot Biocatalytic Synthesis of D-Amino Acids via a Deracemization Cascade Exploiting Amine Transaminase as a Thermodynamic Sinkt
Jang Y, Son S, Shin J-S
Advanced Synthesis and Catalysis, 2026, 368 (9), art. no. e70456. doi: 10.1002/adsc.7045
This study describes a whole-cell biocatalytic cascade for efficient synthesis of D-amino acids from inexpensive racemic substrates. By combining L-amino acid deaminase, D-amino acid transaminase, and an R-selective amine transaminase in compartmentalized Escherichia coli systems, the cascade overcame thermodynamic limitations and achieved >90% yields of D-amino acids. The approach provides a sustainable and scalable strategy for industrial D-amino acid production.
Genuine Directed Evolution In Test Tube (GENie)
Feng L, Mao M, Schwaneberg U
bioRxiv [Preprint]. 2026: 2026.05.04.722721. doi: 10.64898/2026.05.04.72272
A novel test-tube screening platform enables ultrahigh-throughput directed evolution without specialized instrumentation by linking enzyme phenotype and genotype through magnetic beads and engineered Escherichia coli cells. Applied to galactose oxidase, alcohol oxidase, and D-amino acid oxidase, the method rapidly identified variants with dramatically enhanced catalytic efficiency, demonstrating strong potential for enzyme engineering and AI-driven biocatalyst design.
Pyrene-Functionalized Bioinspired (L/D) Amino Acids for Nanoassembly Modulations and Intracellular Cu(II) Detection
Maddeshiya T, Kumar P, Garg N, Luis SV, Pandey MD
Chempluschem. 2026; 91(3):e70138. doi: 10.1002/cplu.70138
This study reports the development of bioinspired chiral nanomaterials incorporating L- and D-amino acids linked to a pyrene fluorophore. The chirality of D-/L-valine and D-/L-phenylalanine modulated nanoassembly behavior and chiroptical properties, enabling intracellular Cu(II) detection. These findings highlight the potential of D- amino acid-based materials for advanced sensing and nanotechnology applications.
Cytosolic PRDX1 acts as an extramitochondrial sink to set mitochondrial H2O2 levels and enable resilience to chronic mitochondrial oxidative stress
Jacobs LJ, Doll S, Trümbach D, Veronese M, Di Pietro G, Yapici FI, Hasberg L, Gentzsch P, Gerlich S, Hansen J, von Karstedt S, Rugarli EI, Conrad M, Salvador A, Riemer J
Redox Biol. 2026; 94:104195. doi: 10.1016/j.redox.2026.104195
The utilization of a magneto-fluorescence sequential labeling strategy for the visualization and tracking of intestinal translocation of oral microbiota
Jing M, Wang X, Li Y, He L, Tan W, Zhang Y, Yang Y, Huang J, Huang Z, Wang C, Niu C
Mater Today Bio. 2026; 38:103062. doi: 10.1016/j.mtbio.2026.103062
This study introduces a D-amino acid-based magneto-fluorescence labeling strategy to trace viable oral microbiota along the oral–gut axis. Using D-alanine-derived probes, researchers successfully tracked bacterial translocation, magnetic separation, and metabolic activity in vivo. These findings provide a powerful new approach to investigate microbiota dynamics and host–microbe interactions influencing systemic health.
Nitrogen Regulates Rice Seedling Growth, Antioxidants, and Metabolites Under Salt Stress
Mai Y, Peng J, Qiu Z, Wu Y, Deng S, Zhang L, Mo Z
Physiol Plant. 2026; 178(2):e70870. doi: 10.1111/ppl.70870
This study shows that nitrogen availability differentially modulates salt tolerance among rice varieties by influencing oxidative stress responses and metabolic pathways. Under salt stress, low nitrogen improved growth and reduced reactive oxygen species in specific cultivars. Metabolomic analyses identified alterations in tryptophan, D-amino acid, and α-linolenic acid metabolism, suggesting that D-amino acid-related pathways contribute to adaptive responses to salinity stress in rice.
Cold plasma treatment induces protein oxidation and nitration, but enhances protein digestibility
Bayati M, Karalia S, Awad NMH, Goksen G, K Tiwari B, M Poojary M
Food Chem. 2026; 514:149081. doi: 10.1016/j.foodchem.2026.149081
This study demonstrates that cold plasma treatment induces oxidation, nitration, and partial racemization of amino acids in animal and plant proteins, leading to the formation of D-amino acids such as D-Ile, D-Leu, and D-Ala. Structural modifications, including reduced α-helical content and increased β-sheets, were associated with improved protein digestibility. These findings provide new insights into how food-processing technologies influence protein chemistry and D-amino acid generation.
D-AAs IN BACTERIA:
D-amino acids inhibit biofilm formation in Escherichia coli and increase antibiotic susceptibility in multidrug-resistant bacteria
Wang J, Yang B, Xing G, Zhao Y, Wu Z, Li J, Qi M, Wu J
Folia Microbiol (Praha). 2026. doi: 10.1007/s12223-026-01493-3
This study shows that multidrug-resistant Escherichia coli isolated from diarrheic lambs frequently forms biofilms, contributing to persistent infections and antibiotic resistance. D-amino acids, particularly D-tyrosine and D-tryptophan, significantly inhibited biofilm formation without affecting bacterial growth, partly through downregulation of biofilm-associated genes (luxS, csgD, pgaC). These findings highlight the therapeutic potential of D-amino acids as adjunct strategies against resistant bacterial infections in livestock.
A distinct gene expression mechanism for D-amino acid utilization in hyperthermophilic archaeon Pyrococcus horikoshii
Kawakami R, Kawase T, Uehara T, Sakuraba H, Matsuzawa T, Hayashi J, Ohshima T
FEBS J. 2026. doi: 10.1111/febs.70545
This study identifies a novel D-amino acid-responsive regulatory mechanism in the hyperthermophilic archaeon Pyrococcus horikoshii. The D-amino acid D-allo-Ile modulates the activity of a feast/famine regulatory protein controlling expression of a broad substrate specificity amino acid racemase (BAR) and a transporter gene. Structural analyses revealed that D-amino acids induce conformational changes that regulate DNA binding, providing new insights into D-amino acid sensing and metabolism in extremophiles.
The Alteromonas macleodii ribosome enables consecutive incorporation of bulky D-amino acids into peptides
Katoh T, Takada H, Sigal M, Suga H
Nucleic Acids Res. 2026; 54(7):gkag341. doi: 10.1093/nar/gkag341
This study identifies the Alteromonas macleodii ribosome as a powerful platform for the efficient ribosomal incorporation of bulky D-amino acids into peptides. Compared with the conventional Escherichia coli ribosome, it enabled multiple and consecutive incorporation of diverse D-amino acids and non-canonical residues, greatly expanding the potential for engineering stable and structurally complex macrocyclic peptides for therapeutic and biotechnological applications.
Identification of Bacteroides acidifaciens as an Arabinoxylan-Responsive Gut Bacterium Using D-Amino Acid Metabolic Probe Technology
He Y, Wei S, Li Q, Gan Y, Sun L, Qiao L, Liu Y, Chen Y, Wang Y, Jin M
J Agric Food Chem. 2026. doi: 10.1021/acs.jafc.5c18002
This study identifies the gut bacterium Bacteroides acidifaciens as a key mediator of arabinoxylan metabolism using D-amino acid metabolic probe technology. Arabinoxylan supplementation reshaped gut microbiota composition, increased short-chain fatty acid production, and improved intestinal barrier integrity. These findings highlight the value of D-amino acid-based approaches to investigate microbiota–diet interactions and support the development of functional foods targeting gut health.
Multi-kingdom biofilms breached: microneedle delivery of metabolically targeted organic silver-photosensitizers for polymicrobial infections in diabetic foot ulcers
Li H, Liu X, Hou C, Fan D, Cheng X, Chen Y, Dong J, Zeng W, Chen F
Mater Horiz. 2026. doi: 10.1039/d6mh00459h
This study demonstrates that D-amino acid-functionalized photosensitizers can effectively target complex polymicrobial biofilms in chronic diabetic foot ulcers. The D-alanine-based probe T-DAla-Ag showed superior microbial labeling and biofilm penetration against Diabetic foot ulcer pathogens, enhancing photodynamic antimicrobial activity and accelerating wound healing. These findings highlight the therapeutic potential of D-amino acid-based targeting strategies for resistant biofilm-associated infections.
D-AAs IN PEPTIDES AND PROTEINS:
Rationally Engineered D-Amino Acid Peptide DT7-3 Combats Multidrug-Resistant Helicobacter pylori via a Novel “Triple-Hit” Mechanism
Yan S, Yan X, Zhao J, Zhou Y, Huang C, Chen Y, Wang J, Zhang J, Han C, Gao Y, Jiang T, Zhu H, Shi H, Li F, Zhao J, Cao M
Microorganisms. 2026; 14(4):744. doi: 10.3390/microorganisms14040744
This study describes the development of DT7-3, an all-D-amino acid antimicrobial peptide with potent activity against multidrug-resistant Helicobacter pylori infection. The incorporation of D-amino acids markedly improved proteolytic stability and antimicrobial efficacy. DT7-3 acts through a multifaceted mechanism involving membrane disruption, inhibition of bacterial adhesion, and suppression of virulence genes, while maintaining low toxicity toward host cells and beneficial microbiota, highlighting its promise as a next-generation anti-H. pylori therapeutic.
Peptide-Based Therapeutics for Alzheimer’s Disease: Medicinal Chemistry, AI-Guided Computational Design, and Blood-Brain Barrier Delivery
Al Khzem AH, Gomaa MS
Drug Des Devel Ther. 2026; 20:597087. doi: 10.2147/DDDT.S597087
This review highlights the growing potential of peptide-based therapeutics for Alzheimer’s disease, emphasizing strategies such as D-amino acid incorporation, cyclization, and peptidomimetic design to improve metabolic stability and blood-brain barrier penetration. Combined with AI-driven peptide design and advanced delivery systems, these approaches may accelerate the development of targeted therapies against amyloid-β aggregation, tau pathology, and neurodegeneration.
Structure-Function Relationships of Amphipathic (Arg-Arg-Aib)(n) Peptides: Impact of Chirality and Chain Length on Membrane Permeability and Nucleic Acid Delivery
Inokuma A, Yokoo H, Demizu Y
Chem Pharm Bull (Tokyo). 2026; 74(3):253-259. doi: 10.1248/cpb.c26-00014
This study demonstrates that incorporating D-amino acids into amphipathic cell-penetrating peptides enhances protease resistance while maintaining efficient membrane permeability and plasmid DNA delivery. Optimized combinations of L/D-arginine residues and Aib (2-aminoisobutyric acid) promoted stable α-helical structures and effective cellular uptake, highlighting the potential of D-amino acid-based CPPs for advanced drug and gene delivery applications.
An antimicrobial peptide based on tryptophan/arginine minimalist design effectively combating multidrug-resistant bacterial infections via dual mechanisms of action
Zou J, Wang J, Gao L, Zhu J, Xue W, Xu N, Yu Q, Gou S, Zhang Y, Liu ., Zhong C, Ni J
Chemical Engineering Journal, 2026, 537, art. no. 176476. doi: 10.1016/j.cej.2026.176476
This study describes the development of wf2, an all-D-amino acid antimicrobial peptide with potent activity against multidrug-resistant bacteria. Incorporation of D-amino acids markedly improved proteolytic stability while preserving strong antimicrobial and anti-biofilm efficacy. The peptide displayed rapid bactericidal activity, low toxicity, and therapeutic efficacy comparable to standard antibiotics in animal infection models, highlighting its translational potential as a next-generation antimicrobial agent.
HighFold-MeD2: An Enhanced Boltz-2 Model for Accurate Structure Prediction of N-Methylated and D-Amino Acid Cyclic Peptides
Cao Z, Wang W, Cao S, Zhang C, Guo J, Duan H
J Chem Inf Model. 2026. doi: 10.1021/acs.jcim.6c00158
This study presents HighFold-MeD2, an AI-based framework for accurate prediction of cyclic peptide structures containing D-amino acids and backbone N-methylated residues. By integrating deep learning, chemical component representations, and diffusion-based modeling, the platform improves the design of metabolically stable and membrane-permeable cyclic peptides, accelerating the development of next-generation peptide therapeutics.
Enhanced proteolytic stability and distinct mechanisms of a D-amino acid- modified antimicrobial peptide against Pseudomonas aeruginosa
Khlaychinda S, Suriya U, Roytrakul S, Aunpad R
Sci Rep. 2026. doi: 10.1038/s41598-026-49275-8
The incorporation of D-amino acids into the antimicrobial peptide dPA-13 markedly improves proteolytic stability and enhances activity against multidrug-resistant Pseudomonas aeruginosa infection. Unlike the parental peptide, dPA-13 efficiently translocates into the bacterial cytoplasm, disrupting both membrane integrity and intracellular homeostasis. It also slows the emergence of bacterial resistance, highlighting the therapeutic potential of D-amino acid-based antimicrobial strategies.
Recent advances in the molecular interactions of anti-cancer peptides with cellular targets
Zaeifi D
Life Sci. 2026: 124454. doi: 10.1016/j.lfs.2026.124454
Anti-cancer peptides (ACPs) are emerging therapeutics that selectively target tumor cells through membrane disruption, intracellular interactions, and immune modulation. The incorporation of D-amino acids improves peptide stability and resistance to proteolytic degradation, enhancing therapeutic efficacy. Advances in cyclisation, nanoparticle delivery, and AI-driven peptide design are accelerating ACP development, with over 80 candidates currently in clinical trials and potential approvals expected within the next few years.
Molecular Engineering of Piezoelectricity in L/L and L/D Amino Acid-Containing Dipeptide Assemblies
Chen C, Mo W, Cheng Y, Tang X, Han F, Yan L, Yu J
ACS Appl Bio Mater. 2026 May 8. doi: 10.1021/acsabm.6c00534
This study demonstrates that incorporating D-amino acids into peptide-based piezoelectric materials enhances supramolecular organization and electromechanical performance. Heterochiral L/D dipeptides showed significantly higher piezoelectric coefficients and energy-harvesting efficiency than all-L counterparts, highlighting the critical role of residue chirality in tuning peptide assembly and functionality for self-powered wearable and implantable biomedical devices.
D-AAs AND ANALYTICAL METHODS (AND FOODS):
Chiral derivatization reagents for enantioselective LC-MS/MS analysis of amino acids with analyte-specific fragmentation
Sakamoto T, Ishikura K, Onozato M, Fukushima T
Journal of Chromatography A, 2026, 1774, art. no. 466851 doi: 10.1016/j.chroma.2026.466851
This study introduces novel chiral derivatization reagents for rapid LC–MS/MS analysis of amino acid enantiomers, enabling simultaneous separation and identification of 37 amino acids within 16 minutes. Application to fermented dairy products revealed the presence of several D-amino acids, including D-Ala, D- Ser, D-Asp, D-Glu, and D-Arg, suggesting that D-amino acids contribute to bacterial metabolism and the sensory properties of fermented foods.
Machine-learning assisted design of ultra-sensitive chiral molecularly-imprinted sensor for detection of D-Serine: A potential Alzheimer biomarker
Mansour SS, Mahmoud AM, Moustafa AA, Nashat NW
Electrochimica Acta, 2026, 554, art. no. 148344. doi: 10.1016/j.electacta.2026.148344
This study presents a green molecularly imprinted polymer (MIP)-based electrochemical sensor for highly selective detection of D-serine, a promising biomarker for Alzheimer’s disease. Using a chiral poly-methyldopa matrix, the sensor discriminated D-serine from its L-enantiomer with high sensitivity and reproducibility, enabling direct analysis in human plasma and supporting the development of point-of-care diagnostic devices for neurodegenerative diseases.
INFORMATION
The D-amino acids International Research Center “DAAIR“ has been established in 2019 with the aim to support and perform scientific research projects and activities on the field of D-amino acids. The Center is aimed to represent a pole of excellence at international level for dissemination and research involving the D-amino acids (Director Silvia Sacchi).
The guiding principle is to support the research projects aimed to investigate the involvement of D-amino acids in main physiological processes, from bacteria to humans. The ultimate goal is the elucidation of the mechanisms by which the D-amino acids perform specific functions, and to identify their presence and concentration in different organisms and compartments, with particular emphasis to pathological states: understand the involvement of D-amino acids in important diseases as a way to set up novel therapeutic strategies.
https://www.d-aminoacids.com/
mailing address: info@d-aminoacids.com
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