Solid-phase peptide synthesis using Nα-trityl-amino acids

The preparation of N-trityl-amino acids is described. Several derivatives of trifunctional amino acidscarrying acid- and base-labile side-chain protecting groups and the trityl group at the N position are prepared for first time. The incorporation of N-trityl-amino acids into peptide sequences usingsolid-phase protocols was achieved. The use of the trityl groupfor the protection of the -amino group in conjunction with base-labile side-chain protecting groups constitutes a newmethod for the assembly of peptides in mild conditions.     

Simultaneous determination of histamine and Nτ-methylhistamine in human plasma and urine by gas chromatography-mass spectrometry

A new and sensitive method is described for the determination of histamine and N^τ-methylhistamine in human plasma and urine by gas chromatography-mass spectrometry. ¹⁵N₂-Labeled histamine and N^τ-[methyl-d₃]methylhistamine were used as internal standards. Histamine and N^τ-methylhistamine were converted to the derivatives N^α-heptafluorobutyryl-N^τ-ethoxycarbonylhistamine and N^α-heptafluorobutyryl-N^τ-methylhistamine, respectively. After these derivatives had been purified on a small column packed with CPG-10, the molecular ions were monitored during selected ion monitoring. Linear standard curves were obtained in the range of 0.5–10 ng/ml for both compounds. The reliability of the histamine analysis was demonstrated by using two different ion pairs, while a comparison with results from two different derivatizations on the same urine sample also established the specificity of the N^τ-methylhistamine analysis. An increase of 1 ng of histamine in the plasma could be precisely determined by the present method. The histamine content of plasma from five normal subjects was determined as 0.83 ÷ 0.37 (S.D.) ng/ml and the N^τ-methylhistamine content in most subjects was below the limits of this measurement. High excretion of histamine was noted in the urine collected in the early morning from a patient with nephritis.     

N6-甲基化腺苷修饰在乳腺癌中的研究进展

表观遗传学在乳腺癌的恶性进展中起到重要作用,其中N⁶-甲基化腺苷(m⁶A)修饰是最丰富的RNA修饰,参与调节乳腺癌细胞恶性行为的通路及癌细胞所处的肿瘤微环境。同时,乳腺癌发病率居于我国女性恶性肿瘤首位,近年来首次发病年龄趋于年轻化,是严重危及我国女性健康的疾病之一。然而,乳腺癌早期治疗预后较好。当晚期出现转移后,患者5年生存率差。m⁶A作为一种可能用于乳腺癌早筛的生物标志物及新的药物治疗靶点,给乳腺癌的早期治疗提供了新的研究方向。本文系统地综述了m⁶A修饰相关因子及其在乳腺癌恶性行为中发挥的调控作用,并列出现已知的一些靶向药物和潜在的早筛方法,为乳腺癌的诊断、治疗、监测提供新的思路。     

基因工程菌发酵合成L－苏氨酸－N15

采用含有稳定同位素^１５Ｎ－硫酸铵为主要氮源的专用发酵培养基配方和提取精制条件,在国内、外首次采用基因工程菌ＡＡ_７（ｐ^ＴＨ２）（ＡＨＶ^ｒＡＥＣ^ｒ,Ｔｈ^ｒ－Ｎ^－,Ｈｏｍ^ｒ,Ａｐ^ｒ）直接发酵方法研制Ｌ－苏氨酸－Ｎ^１５高丰度精制产品。每ｍｏｌ^１５Ｎ－硫酸铵实际得到０．６３８ｍ     

N6-甲基腺苷修饰(m6A)在乳腺癌中的研究进展

乳腺癌是女性最常见的癌症之一,也是导致女性癌症死亡的最主要原因.尽管早期乳腺癌的治疗已经取得了极大进展,但晚期伴转移乳腺癌治疗效果较差,具有高复发率和高死亡率.因此,鉴定新的用于诊断和预测乳腺癌转移的分子标记、开发新的治疗策略成为迫切需要.近年来,mRNA的异常N⁶-甲基腺苷修饰(N⁶-methyladenosine,m⁶A)对癌基因功能和表达水平的表观遗传学调控逐渐成为恶性乳腺癌研究的焦点.本文分析和总结了m⁶A甲基化修饰及其调节蛋白参与调控乳腺癌发生发展的最新研究进展,以期为乳腺癌中m⁶A甲基化修饰研究提供新的思路和参考,进一步为乳腺癌的诊断、治疗、预后及监测提供新的有效策略.     

N6-甲基腺苷修饰对女性生殖系统功能的影响

近年来女性不孕不育率不断攀升，已成为我国提高生育率亟需解决的困境。生殖系统的健康是保证生育能力的前提条件。N ⁶-甲基腺苷(N⁶-methyladenosine,m⁶A)是真核生物中最常见的化学修饰，在细胞生命活动中发挥着极其重要的作用。近来，m⁶A修饰被证实在女性生殖系统的各种生理和病理过程中起着关键作用，但其调控机制及生物学功能仍不清楚。本文首先介绍了m⁶A修饰的可逆调节机制及其功能，随后讨论了其在女性生殖功能和生殖系统疾病中的作用，最后对m⁶A修饰的检测技术和方法及其最新进展进行了归纳总结，以期为后续女性生殖系统发病机制和治疗研究提供参考。     

Molecular and crystal structure of Nα-(9-fluorenyl)- methoxycarbonyl-L-ornithine hydrochloride diethyl ether solvate

The solid-state conformation of the first N-protected ornithine derivative has been established by X-ray analysis. The hydrochloride of N-(9-fluorenyl)methoxycarbonyl-L-ornithine crystallises as diethyl ether solvate. The backbone (₀, , , ¹) torsion angles are (174.9°, –84.0°, 145.9°, –171.0°). The conformation of the urethane amide bond is trans. The ornithine aliphatic side chain adopts preferred fully extended conformation which is stabilised by the hydrogen bonding of the –NH₃ ⁺ group to the diethyl ether molecule, carboxyl group and Cl^- anions.     

The mimics of Nε-acyl-lysine derived from cysteine as sirtuin inhibitors

Sirtuin inhibitors as physiological research tools and therapeutic potentials have caught many attentions in last decades. The mimics of acyl lysine have been approved to be a very efficient strategy for development of mechanism-based sirtuin inhibitors. In current study, a novel scaffold of l-S-(3-carboxamidopropyl) cysteine (l-CAPC) has been exploited for design and synthesis of sirtuin inhibitors. As a result, the mimics of N^ε-acyl-lysine derived from cysteine including small molecules (5a–m) and peptides (9a–m) have been synthesized. Among these, the peptides 9g and 9h were found to be the most inhibitory potency and selectivity against SIRT2.     

N6-甲基化腺嘌呤RNA甲基化修饰在中枢神经系统中的作用研究进展

mRNA存在多种转录后修饰,这些修饰调控mRNA的稳定和剪接、翻译、转运等多个过程,进而影响细胞发育、机体免疫、学习认知等重要生理功能。其中m⁶A修饰是转录后修饰中最丰富的一种,广泛存在于mRNA中,调控mRNA的代谢活动,影响基因表达。m⁶A修饰的稳态对神经系统的发育和功能维持至关重要。近年研究发现,在神经退行性疾病、精神疾病和脑肿瘤中均存在m⁶A修饰的身影。因此本文对近几年m⁶A甲基化修饰在中枢神经系统发育、功能及相关疾病中的作用进行总结,为神经系统疾病提供潜在的临床治疗靶点。     

N+离子注入热带假丝酵母对长链二元酸产量的影响*

用热带假丝酵母（Ｃａｎｄｉｄａ ｔｒｏｐｉｃａｌｉｓ）ＳＣＢ４１２作为出发菌株,经能量５０ＫｅＶ、剂量１× １０^１１～５ ×１０^１５ ｉｏｎｓ／ｃｍ^２的Ｎ^＋离子注入诱变处理,以产生可遗传的诱变。 Ｎ^＋离子注入后,存活率与剂量呈指数衰减关系：ｌｏｇ（存活率％）＝ ８．２３－ ０．６０４ × ｌｏｇ（剂量）,在培养过程中可观察到酵母菌菌落和细胞形态均发生了变化。经筛选,获得了一株能够利用     

N6-腺苷酸甲基化修饰在脂质代谢紊乱疾病中调控作用研究进展

脂质代谢是一个复杂的生理过程,与营养调节、激素平衡和内分泌作用密切相关,它涉及多种因子和信号转导通路的互作。脂质代谢紊乱是诱发多种疾病的主要机制之一,如肥胖症、糖尿病、非酒精性脂肪肝病、肝炎、肝细胞癌及其并发症等。目前越来越多的研究发现RNA上发生的N⁶-腺苷酸甲基化(N⁶-adenylate methylation, m⁶A)“动态修饰”代表了一种全新的“转录后”调控方式,mRNA、tRNA、ncRNA等均可发生m⁶A修饰,m⁶A修饰异常调控基因表达变化和可变剪切事件发生。据最新文献报道,m⁶ARNA修饰参与了脂质代谢紊乱的表观遗传学调控。本文基于脂质代谢紊乱诱发的主要疾病,综述m⁶A修饰在其发生和发展中的调控作用。这些发现从表观遗传学的角度为进一步深入研究脂质代谢紊乱发病的潜在分子机制提供了依据,为相关疾病的卫生预防、分子诊断和治疗提供参考。     

粉被虫草N6-(2-羟乙基)腺苷高产菌株的原生质体诱变育种*

在粉被虫草(Cordyceps prainosa Petch)无性型——粉被马利娅霉(Mariannaeapruinosa Liang)原生质体形成和再生的前期研究基础上,报道了通过原生质体诱变培育高产N⁶-(2-羟乙基)腺苷菌株的研究结果。粉被马利娅霉Cp-14单孢子株经15W紫外灯照射后,获得一高产突变株MpM-135．经多代移植后,此突变株比出发菌株Cp-14的N⁶-(2-羟乙基)腺苷含量提高了14.8％。实验还表明,粉被虫草无性型菌丝提取物对枯草杆菌(Bacillussubtilis)抗紫外辐射效果与菌丝所含N⁶-(2-羟乙基)腺苷含量有正相关性。     

黄土高原旱塬区陇东苜蓿草地N2O释放动态及微生物驱动因子的研究

在甘肃庆阳黄土高原,采用静态箱-气相色谱法测定了3年龄陇东苜蓿草地不同物候期的N²O释放通量,采用最大或然数法(MPN)测定了土壤0～30 cm硝化细菌和反硝化细菌数量,探讨旱区紫花苜蓿草地N²O释放规律与其土壤微生物的关系。结果表明:（1）3年龄陇东苜蓿草地年内N²O释放通量在-0.099～0.085 mg·m^-2·h^-1之间;N²O释放通量在头茬花期和越冬前再生期达到高峰,而二茬再生期和越冬期则处于N²O吸收期,成为N²O贮存库。（2）陇东苜蓿草地亚硝酸细菌、硝酸细菌和反硝化细菌数量在不同物候期和土壤层次间存在差异。（3）3年龄陇东苜蓿草地N²O释放通量与土壤水分含量、土壤pH、硝酸细菌和反硝化细菌数量间呈显著正相关线性关系。（4）庆阳黄土高原旱区陇东苜蓿草地是较弱的农业N²O释放源,远低于同类研究和国际释放平均水平。     

Potential difference responses due to K+, Na+ and Cl− changes in Bullfrog antrum with and without HCO3−

The effect of changing [K⁺], [Na⁺] and [Cl^?] in nutrient solution was studied in bullfrog antrum with and without HCO₃^? in nutrient. In 25 mM HCO₃^? (95% O₂/5% CO₂) and in zero HCO₃^? (100% O₂), nutrient pH was maintained at 7.3. Changing from 4 to 40 mM K⁺ or from 81 to 8.1 mM Cl^? gave a decrease 10 min later in transmucosal PD (nutrient became more negative) — a normal response. These responses were less in zero than in 25 mM HCO₃^?. A decrease from 102 to 8 mM Na⁺ decreased PD (anomalous response of electrogenic NaCl symport). This effect was attenuated or eliminated in zero HCO₃^?. In contrast, change from 4 to 40 mM K⁺ gave initial anomalous PD response and change from 102 to 8 mM Na⁺, initial normal PD response with either zero or 25 mM HCO₃^?. Both responses were associated with (Na⁺ + K⁺)-ATPase pump and were greater in zero than in 25 mM HCO₃^?. Initial PD increases in zero HCO₃^? are explained as due to increase in the resistance of passive conductance and/or NaCl symport pathways. Thus, removal of HCO₃^? modifies conductance pathways of nutrient membrane.     

The effects of prostaglandins E2 and F2α on synaptosomal accumulation and release of 3H-norepinephrine

Prostaglandins (PG) of both the E and F series may serve as modulators of norepinephrine (NE) release from peripheral sympathetic neurons. We have studied the effects of PGE₂ and PGF_2α on the accumulation and release of ³H-NE in the CNS using synaptosomes isolated from rat hypothalami.The release of ³H-NE from synaptosomes superfused with Krebs-Ringer bicarbonate buffer was multiphasic with an initial fast release phase followed by a slower release. Raising KC1 concentration of the superfusion medium to 56mM during the slow release phase is known to stimulate ³H-NE release. PGE₂ (1 × 10^?6M) attenuated ³H-NE release during the fast phase and reduced the amount of ³H-NE released due to KC1 stimulation. At lower concentrations of PGE₂ there was no change in the release profile. PGF_2α was without effect on ³H-NE release at all concentrations tested.The accumulation of ³H-NE was significantly diminished by PGE₂ at a concentration of 1 × 10^?6M, while a lower concentration (1 × 10^?7M) was ineffective. PGF_2α had no effect on ³H-NE accumulation at all concentrations investigated.