Amino Acids最新文献

{"title":"Aromatic amino acid–metal ion interactions: comparative effects of alkali and Zn2+ on acidity and coordination behavior via QM studies","authors":"Sepideh Kalhor,&nbsp;Alireza Fattahi","doi":"10.1007/s00726-025-03486-x","DOIUrl":"10.1007/s00726-025-03486-x","url":null,"abstract":"<div><p>Among the 20 standard amino acids, aromatic amino acids hold particular importance due to their crucial roles in protein–protein interactions. These residues, including phenylalanine, tyrosine, tryptophan, and histidine, contribute significantly to protein structure and function through their ability to engage in non-covalent interactions, such as π–π stacking and cation–π interactions. In addition, the acid–base duality of aromatic amino acids makes their interactions with metal ions particularly valuable. These interactions are implicated in several essential biological processes, including protein biosynthesis, enzyme catalysis, and molecular recognition. While the interactions between transition metal ions and amino acids have been extensively studied and well-documented, the role of alkali metal ions in similar contexts has received comparatively less attention. However, their influence on amino acid coordination and stability cannot be overlooked, especially given their biological relevance in processes such as ionic regulation, enzyme activation, and membrane transport. The results of this study demonstrate that the complexation of aromatic amino acids with alkali metal ions enhances their acidity. Additionally, we examined the detailed interactions of these metals with the aromatic amino acids.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03486-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel octapeptide containing the RGD sequence as a potential anti-SARS-CoV-2 agent: design, synthesis, and theoretical studies","authors":"Reiner Lemos,&nbsp;Orlando Ortiz,&nbsp;Luis Almagro,&nbsp;Kamil Makowski,&nbsp;Hortensia Rodríguez,&nbsp;Fernando Albericio,&nbsp;Margarita Suarez","doi":"10.1007/s00726-025-03480-3","DOIUrl":"10.1007/s00726-025-03480-3","url":null,"abstract":"<div><p>The design of peptide-based inhibitors targeting cell receptors represents a promising strategy in the development of antiviral agents. In this study, a novel octapeptide containing the RGD sequence was rationally designed to explore its potential interaction with integrins. The peptide was functionalized with a malonic moiety to enhance its binding capabilities and potential bioactivity. Conformational and physicochemical properties were evaluated using DFT-PBEh-3c calculations. Molecular docking studies revealed favorable interactions with the integrin α₅β₁, including coordination with the Mg²⁺ ion at the active site. The peptide was successfully synthesized via Fmoc-based solid-phase peptide synthesis (SPPS) and fully characterized by NMR, IR, MS, and RP-HPLC.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03480-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential amino acid supplementation for pressure ulcers: pathophysiological rationale and results from a pilot study","authors":"Maciej Świątkiewicz,&nbsp;Andrzej Lejczak,&nbsp;Piotr Foltyński,&nbsp;Paweł Grieb","doi":"10.1007/s00726-025-03489-8","DOIUrl":"10.1007/s00726-025-03489-8","url":null,"abstract":"<div><p>Pressure ulcers (PU) are a major and serious problem affecting millions of people. Malnutrition, frequently co-occurring with PU, is considered modifiable risk factor, and dietary supplements currently recommended for supporting PU healing contain a high amount of protein and some additives (zinc, vitamin C, arginine). Unfortunately, many patients with PU suffer from chronic kidney disease and would not tolerate a high-protein diet. Amino acid profiling of the blood serum of PU patients has shown decreased concentrations of exogenous amino acids histidine, tryptophan and threonine. Their common feature is a low daily requirement, 4 to 15 mg/kg body weight. In animal experiments, various types of stress increase metabolic demand for these amino acids. On the other hand, stress significantly slows down wound healing, both in animals and in humans. Considering these observations, a pilot clinical trial in the quasi-experimental design has been performed to assess the effect of Pellicar-F, a proprietary food composition containing histidine in the form of carnosine, plus tryptophan and threonine on PU control. After six weeks patients receiving daily doses of the aforementioned food composition, compared to control patients, displayed statistically significant reduction of the pressure ulcer area. Further evaluation of this product in pressure ulcers and other chronic wounds is indicated.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03489-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145510409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding incretin resistance: a mechanistic framework to reclassify therapeutic variability for GLP-1 receptor agonist therapy","authors":"Almir Fajkić,&nbsp;Yun Wah Lam,&nbsp;Andrej Belančić","doi":"10.1007/s00726-025-03488-9","DOIUrl":"10.1007/s00726-025-03488-9","url":null,"abstract":"<div><p>This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance—receptor-level, post-receptor, and secretory—highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified ‘non-responder’ classification.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03488-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145510408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intelligent design and synthesis of nucleobase and amino acid-based ligands to inhibit the JAK2 enzyme to treat rheumatoid arthritis","authors":"Ameneh Zarei,&nbsp;Alireza Fatahi","doi":"10.1007/s00726-025-03487-w","DOIUrl":"10.1007/s00726-025-03487-w","url":null,"abstract":"<div><p>Rheumatoid arthritis is the most prevalent form of autoimmune arthritis. In modern drug development, computer-aided drug design plays a crucial role not only in discovering new therapeutic compounds but also in assessing their potential efficacy. This study employs ligand-based pharmacophore modeling to identify novel drug candidates without requiring an initial target protein structure. Essential chemical features were extracted from nucleotides, amino acids, and sulfonylaziridine derivatives to construct potential drug scaffolds. Ligands exhibiting similar structural characteristics were then screened for promising chemical interactions. Using MATLAB software, the initial pool of 4,000 candidates was narrowed down to 330, which was further reduced to 58 and finally to 8 through AutoDock screening. These top candidates were further analyzed using molecular docking (static analysis) and molecular dynamics simulations (dynamic analysis). Among them, the compound CPROSCP demonstrated favorable dynamic stability, an appropriate hydrodynamic radius, minimal distortion of protein structure, and advantageous binding energy. The synthesized drug candidate achieved a yield of approximately 92%, with IR and NMR spectroscopy confirming its successful synthesis and high purity.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03487-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145456368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial protection by acidic amino acids and natural dipeptides: potential for an underused resource","authors":"N. King","doi":"10.1007/s00726-025-03485-y","DOIUrl":"10.1007/s00726-025-03485-y","url":null,"abstract":"<div><p>Stopping then restarting the blood flow to the heart can cause ischaemia reperfusion (IR) injury. This can happen during revascularisation following a myocardial infarction and during on pump cardiac surgery using cardioplegic arrest. Despite extensive studies to identify cardioprotective interventions, the myocardium continues to sustain significant injury. Therefore, there is a need to identify agents that can be used during IR. This review focuses on the potential cardioprotective role for acidic amino acids and natural dipeptides using evidence from experimental studies and clinical trials with particular emphasis on their membrane transport. Acidic amino acids are present at high concentration in the heart with a large tissue to plasma concentration gradient, where they are involved in protein synthesis and intermediary metabolism. During cardiac insults they are lost from heart cells but replenishment leads to cardioprotection through energy provision, protection against the production of reactive oxygen species production and improved calcium homeostasis. One important determinant of the intracellular concentration of acidic amino acids and natural dipeptides is membrane transport. The expression and activity of the acidic amino acids transporters EAAT1-3 and the dipeptide transporter, PEPT2 have been demonstrated in membrane vesicles and isolated cardiomyocytes. Improvements in our understanding of these different transport mechanisms should lead to the maximisation of acidic amino acid and natural dipeptide uptake during IR leading to improved cardioprotection.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03485-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant amino acid analogues as antimicrobial agents","authors":"Dmytro Demash,&nbsp;Olena Stasyk,&nbsp;Oleh Stasyk","doi":"10.1007/s00726-025-03484-z","DOIUrl":"10.1007/s00726-025-03484-z","url":null,"abstract":"<div><p>Plants are known as a source of different biologically active compounds, which are uncommon for other kingdoms of life. Among them are different amino acid analogues, which are synthesized and accumulated in certain plants as a passive defense mechanism against herbivorous insects and grazing mammals. As a rule, cell protein synthesis machinery of herbivores cannot effectively differentiate between standard proteinogenic amino acids and their specific plant analogues, resulting in misincorporation of the latter into nascent proteins and their malfunctioning, which constitutes a mechanism of plant defense. Examples of such amino acids are analogues of arginine (canavanine, indospicine), proline (azetidine-2-carboxylic acid), and cysteine/lysine (thialyasine). This review summarizes existing knowledge on these and other related amino acids as potential antibacterial and antifungal agents, including their possible targets and known resistance mechanisms. We also discuss the possibility of using amino acid analogues as sole antimicrobial agents or in combination with known antibacterials and antifungals. We also propose a strategy of enhancing the antimicrobial activity of amino acid analogue by concomitant starvation for the corresponding standard amino acid, which has been proven efficient in anticancer studies. Such an approach might potentially help to overcome, at least partially, microbial resistance to known antibiotics, especially when such resistance relies on increased protein synthesis in pathogen cells.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03484-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysine malonylation as a therapeutic target: implications for metabolic, inflammatory, and oncological disorders","authors":"Ahsanullah Unar","doi":"10.1007/s00726-025-03483-0","DOIUrl":"10.1007/s00726-025-03483-0","url":null,"abstract":"<div><p>Lysine malonylation (Kmal) is an emerging posttranslational modification (PTM) intricately linked to cellular metabolism and disease pathogenesis. This review explores the regulatory mechanisms of Kmal, emphasizing the role of malonyl-CoA as its donor substrate and Sirtuin 5 (SIRT5) as its primary demalonylase. Kmal significantly influences metabolic homeostasis, inflammation, and cancer by modifying key enzymes involved in glycolysis, fatty acid oxidation, and mitochondrial function. In metabolic disorders such as type 2 diabetes and obesity, aberrant malonylation contributes to insulin resistance, lipid accumulation, and oxidative stress. Inflammatory conditions, including sepsis and autoimmune diseases, involve malonylation-driven regulation of immune responses, particularly through GAPDH-mediated cytokine translation. Furthermore, in oncogenesis, malonylation plays a dual role: it suppresses tumor growth by impairing metabolic flux while also being exploited by cancer cells to maintain proliferation. Therapeutic interventions targeting Kmal include SIRT5 modulators, malonyl-CoA metabolism regulators, and small-molecule inhibitors that modulate lysine acylation dynamics. Advances in mass spectrometry and proteomics have expanded our understanding of the biological functions of Kmal; however, its full physiological and pathological significance remains under investigation. Future research should focus on elucidating tissue-specific malonylation patterns and their interactions with other PTMs to refine therapeutic strategies. By integrating metabolic regulation with disease mechanisms, Kmal has emerged as a crucial biochemical modification with broad implications for metabolic, inflammatory, and oncological disorders. Understanding its regulatory network will be pivotal in developing precision medicine approaches aimed at mitigating disease progression and restoring cellular homeostasis.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03483-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of processing of canola protein isolate on postprandial plasma amino acid profiles in healthy, young females","authors":"Noortje Boot,&nbsp;Wesley J. H. Hermans,&nbsp;Ines Warnke,&nbsp;Alex Overman,&nbsp;Janneau M. X. van Kranenburg,&nbsp;Joan M. Senden,&nbsp;Lex B. Verdijk,&nbsp;Luc J. C. van Loon","doi":"10.1007/s00726-025-03482-1","DOIUrl":"10.1007/s00726-025-03482-1","url":null,"abstract":"<div><p>Canola protein is a rapeseed-derived protein that contains all essential amino acids in proportions that meet the WHO amino acid scoring requirements, making it an interesting protein for human food applications. It is currently unknown whether canola protein processing modulates postprandial plasma amino acid bioavailability in vivo in humans. This study compared postprandial plasma amino acid profiles following the ingestion of unprocessed (native) canola, processed canola, and whey protein isolate in healthy, young, females. In a randomized, clinical, cross-over design, 15 healthy young females (25 ± 3 y) participated in four test days on which they consumed 20 g protein as either native canola, enzyme processed or heat processed canola protein, or 20 g whey protein. Blood samples were collected for 5 h following protein ingestion to assess plasma amino acid concentrations. Ingestion of native canola protein resulted in lower increases in plasma total amino acid (TAA) concentrations compared to whey protein (3191 ± 794 vs. 4429 ± 84 µmol∙L^− 1, <i>P</i> &lt; 0.001). Canola protein processing resulted in greater peak plasma total amino acids concentrations, reaching statistical significance for enzyme (3599 ± 687 µmol∙L^− 1, <i>P</i> = 0.045) but not heat (3565 ± 722 µmol∙L^− 1, <i>P</i> = 0.166) treated compared to native canola protein. Plasma total amino acid availability, expressed as incremental area under the curve over a 5 h postprandial period, did not differ between treatments and averaged 163 ± 81, 171 ± 76, 194 ± 82, and 207 ± 85 mmol∙300 min∙L^− 1 following ingestion of native, enzyme- and heat processed canola, and whey protein, respectively (<i>P &gt; 0.05</i>). Ingestion of whey protein allows for a more rapid postprandial rise in circulating essential and non-essential amino acids and greater postprandial plasma total amino acid availability when compared to the ingestion of native canola protein. Ingestion of enzyme- or heat processed canola protein accelerates the postprandial rise in circulating amino acids but does not further augment overall plasma amino acid availability throughout a 5 h postprandial period when compared to the ingestion of native canola protein.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03482-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring claudin proteins: from sequence motifs to their impact on tight junction-mediated signaling pathways","authors":"Lingling Bao,&nbsp;Siqi Yang,&nbsp;Wenhua Zhao,&nbsp;Yongchun Zuo","doi":"10.1007/s00726-025-03479-w","DOIUrl":"10.1007/s00726-025-03479-w","url":null,"abstract":"<div><p>Claudin (CLDN) proteins are extensively studied due to their critical role in maintaining tissue barriers and cell polarity. However, significant gaps remain in understanding the functional mechanisms of their sequence motifs and the molecular mechanisms of their interactions with other tight junction proteins<b>.</b> This review systematically examines the multifunctional properties of the CLDN protein family from the perspectives of sequence and structure. During evolution, CLDN family members have developed highly conserved structural features, particularly key conserved sites within the first extracellular loop (ECL1) and the C-terminal PDZ-binding domain, which play a central role in regulating the barrier function of tight junctions, ion selectivity, and protein–protein interactions. Furthermore, the distribution pattern of acidic and basic amino acids in ECL1 has been shown to directly determine ion selectivity and paracellular permeability. Meanwhile, the assembly and functional stability of tight junctions are precisely regulated by the C-terminal PDZ-binding domain through its interactions with the ZO protein family. Additionally, the study further elucidates how CLDN proteins modulate critical signaling pathways governing cellular proliferation, survival, and permeability, thereby participating in diverse physiological and pathological processes. These insights have deepened the understanding of the functional diversity of CLDN proteins and provided a new theoretical basis for developing disease diagnostic markers and designing targeted treatment strategies based on CLDN proteins.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-025-03479-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}