bims-polyam 2024-05-12 papers

Issue of 2024–05–12
three papers selected by
Sebastian J. Hofer, University of Graz

RSC Chem Biol. 2024 May 08. 5(5): 467-472

Polyamines promote xenobiotic nucleic acid synthesis by modified thermophilic polymerase mutants.

Hidekazu Hoshino, Yuuya Kasahara, Satoshi Obika.

The enzymatic synthesis of xenobiotic nucleic acids (XNA), which are artificially sugar-modified nucleic acids, is essential for the preparation of XNA libraries. XNA libraries are used in the in vitro selection of XNA aptamers and enzymes (XNAzymes). Efficient enzymatic synthesis of various XNAs can enable the screening of high-quality XNA aptamers and XNAzymes by expanding the diversity of XNA libraries and adding a variety of properties to XNA aptamers and XNAzymes. However, XNAs that form unstable duplexes with DNA, such as arabino nucleic acid (ANA), may dissociate during enzyme synthesis at temperatures suitable for thermophilic polymerases. Thus, such XNAs are not efficiently synthesised by the thermophilic polymerase mutants at the end of the sequence. This undesirable bias reduces the possibility of generating high-quality XNA aptamers and XNAzymes. Here, we demonstrate that polyamine-induced DNA/ANA duplex stabilisation promotes ANA synthesis that is catalysed by thermophilic polymerase mutants. Several polyamines, including spermine, spermidine, cadaverine, and putrescine promote ANA synthesis. The negative effect of polyamines on the fidelity of ANA synthesis was negligible. We also showed that polyamines promote the synthesis of other XNAs, including 2'-amino-RNA/2'-fluoro-RNA mixture and 2'-O-methyl-RNA. In addition, we found that polyamine promotes DNA synthesis from the 2'-O-methyl-RNA template. Polyamines, with the use of thermophilic polymerase mutants, may allow further development of XNA aptamers and XNAzymes by promoting the transcription and reverse transcription of XNAs.

DOI: https://doi.org/10.1039/d4cb00017j

J Affect Disord. 2024 May 08. pii: S0165-0327(24)00759-6. [Epub ahead of print]

Association between dietary spermidine intake and depressive symptoms among US adults: National Health and Nutrition Examination Survey (NHANES) 2005-2014.

Guolian Qi, Jianing Wang, Yunyan Chen, Wei Wei, Changhao Sun.

BACKGROUND: Spermidine (SPD) has a number of advantageous effects, including life extension and neuroprotection. However, few observational studies have investigated the association of dietary SPD intake with depression.
METHODS: We used data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) and the corresponding Food Patterns Equivalents Database (FPED). SPD content of food groups from published data were merged with the appropriate FPED data to estimate the SPD intake for each subject. Patients with Patient Health Questionnaire-9 (PHQ-9) scores of 10 or above were thought to experience clinically relevant depression symptoms. Logistic regression, sensitivity analysis, and restricted cubic spline (RCS) were used.
RESULTS: Among the 19,306 participants, the overall prevalence of depression was 8.72 %. After controlling for relevant confounders, individuals in the highest tertile or quartile of total SPD and SPD derived from fruits, vegetables, cereals, nuts, eggs and seafood had a significantly lower prevalence of depression (OR total SPD = 0.77, 95 % CI: 0.63-0.93); OR fruit-sourced SPD = 0.81, 95 % CI: 0.68-0.95; OR vegetable-sourced SPD = 0.72, 95 % CI: 0.61-0.85; OR cereals-sourced SPD = 0.73,95 % CI:0.60-0.88; OR nuts- sourced SPD = 0.80, 95 % CI: 0.71-0.91; OR egg-sourced = 0.72, 95 % CI: 0.62-0.84 and OR seafood-sourced SPD = 0.65, 95 % CI: 0.55-0.77) comparing those in the lowest tertile or quartile.
CONCLOUSION: Our fndings reveal a negative association between dietary SPD intake and depression.

Keywords: Autophagy; Depression; Dietary spermidine; NHANES

DOI: https://doi.org/10.1016/j.jad.2024.05.041

Nucl Med Biol. 2024 Apr 26. pii: S0969-8051(24)00041-6. [Epub ahead of print]134-135 108915

Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging.

Kaixin Qin, Dongmei Shi, Yuzhou Zheng, Wenhao Hu, Xiameng Kang, Ping Wu, Xinzhong Hao, Haiyan Liu, Jie Gao, Jianguo Li, Zhifang Wu, Sijin Li, Hongliang Wang.

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor.
RESULTS: The radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71.
CONCLUSION: These results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

Keywords: Gallium-68; Molecular probe; PET/CT; Polyamine metabolism; Radiolabeling

DOI: https://doi.org/10.1016/j.nucmedbio.2024.108915