N-Methyl peptides

The natural occurrence of N-methyl peptides in various plant metabolites has made N-methylation a subtle and attractive possible modification for structure-activity relationship studies of endogeneous peptides. However, little is known about the conformational specificity induced by the N-methylation of a given peptide, and particularly concerning the β-turn conformation. A spectroscopic investigation (i.r., n.m.r., CD) and X-ray diffraction experiments have been carried out on tBuCO-X-Me-Y-NHMe blocked dipeptides (X = Gly, L-Ala, L-Pro, and Y = Gly, and L- or D-Ala, Leu, Phe) with reference to the homologous desmethylated species. The influence of the N-methylation on conformation depends to a large extent on the chirality of the X and Y residues. Homochiral sequences are the most affected, with a strong preference for the βVI-folded conformation containing a middle cis amide bond. Heterochiral sequences are essentially unaffected and retain the βII-folded conformation with a trans middle amide bond. Glycine-containing sequences undergo a more complex perturbation according to the X or Y position of the Gly residue. The available data for larger N-methyl peptides are consistent with our observations, suggesting that these simple dipeptides well reflect the conformational perturbations induced by N-methylation on the β-turn conformation.     

Applications of ammonium formate-catalytic transfer hydrogenation.

Dehalogenation of chlorine bound to aromatic nuclei has been achieved using ammonium formate-catalytic transfer hydrogenation (AF-CTH) techniques. The use of deuterated ammonium formate as the transfer agent in the CTH process when performed in a deuterated solvent medium results in the predominant formation of the labeled product. Thus, ND₄+ DCOO^- - CTH of [D-Ala², p-ClPhe⁴]-Leu-enkephalin in 80% CD₃COOD/D₂O yielded [D-Ala², Phe (4D)⁴]-Leu-enkephalin. Levels of D-incorporation were measured by fast atom bombardment-mass spectrometry (FAB-MS) and/or by ¹³C n.m.r. spectroscopy. Using D-labeled and unlabeled ammonium formate in stoichiometrically similar reactions, it was concluded that the hydrogenation exhibited a primary kinetic isotope effect. Reactant and product concentrations were determined by amino acid analysis and reversed phase HPLC.     

肾小管细胞氧化性损伤模型的建立

目的建立过氧化氢(H2O2)所致肾小管氧化性损伤模型。方法利用离体培养肾小管细胞建立氧化性损伤模型．观察肾小管细胞形态结构的改变及细胞存活率、乳酸脱氢酶(lactated dehydrogenase，LDH)释放率、脂质过氧化产物丙二醛(malondialdehyde．MDA)含量的变化，以及还原型谷胱甘肽的保护作用。结果H2O2所致肾小管细胞损伤．表现为细胞存活率降低，LDH释放增加和MDA含量增加。还原型谷胱甘肽能提高细胞存活率，降低LDH释放，减轻脂质过氧化反应。结论H2O2可复制离体肾小管氧化性损伤模型．还原型谷胱甘肽对损伤的肾小管上皮细胞有保护作用。     

丁基苯酞对正常及局部脑缺血大鼠纹状体脑血流影响

应用氢清除法连续测定大鼠一侧纹状体脑血流量(rCBF), 并观察丁基苯酞(NBP)对其影响. 结果表明, NBP 40或80 mg·kg^-1 ig均能显著增加大脑中动脉阻断后纹状体的rCBF(与溶剂对照组相比P<0.01), 作用持续3 h. 此外, 5-20 mg·kg^-1 ig时, 也可增加正常大鼠纹状体脑血流, 各剂量组NBP对平均动脉压均无明显影响; 尼莫地平(Nim)0.5 mg·kg^-1 ip也能明显增加纹状体脑血流, 同时轻度降低动脉平均压, 其增加脑血流作用与NBP 5 mg·kg^-1的作用相当. 提示NBP不仅能增加正常大鼠纹状体的脑血流, 还能增加大脑中动脉阻断后纹状体的血流量, 其抗脑缺血作用可能与该作用有关.     

过氧化氢在大鼠心脏缺氧再灌注时的细胞化学定位

目的：研究心肌缺氧再灌注时过氧化氢的产生部位。方法：以大鼠为实验动物，CeCl3为捕捉剂，用细胞化学的方法进行检测，并用X－射线能谱分析的方法对沉淀颗粒进行元素分析。结果：血管内皮细胞及部分心肌的线粒体肿胀。内皮细胞腔面、基底膜、肌细胞膜都有沉淀颗粒，以血管内皮细胞腔面最多。结论：缺氧再灌注时，不仅损伤内皮细胞，而且损伤至每一个心肌细胞。     

Monoclinic polymorph of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe(anhydrous)

The structures of two crystal forms of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe have been determined. The triclinic form (PI, Z= l) from DMSO/H₂O crystallizes as a dihydrate (Karle, Sukumar & Balaram (1986) Proc. Natl. Acad. Sci. USA 83, 9284-9288). The monoclinic form (P2¹, Z = 2) crystallized from dioxane is anhydrous. The conformation of the peptide is essentially the same in both crystal systems, but small changes in conformational angles are associated with a shift of the helix from a predominantly α-type to a predominantly 3₁₀-type. The r.m.s. deviation of 33 atoms in the backbone and Cβ positions of residues 2-8 is only 0.29 Å between molecules in the two polymorphs. In both space groups, the helical molecules pack in a parallel fashion, rather than antiparallel. The only intermolecular hydrogen bonding is head-to-tail between helices. There are no lateral hydrogen bonds. In the P2₁ cell, a = 9.422(2)Å, b = 36.392(11)Å, c = 10.548(2)Å, β= 111.31(2)° and V = 3369.3ų For 2 molecules of C⁶⁰H⁹⁷N¹¹O¹⁰ per cell.     

Clinical report on 62 cases of acute dimethyl sulfate intoxication

Sixty-two cases of accidental acute intoxication from the inhalation of dimethyl sulfate (DMS) are reported. To facilitate clinical evaluation and treatment, as well as identification of capacity for physical labor, a grading system was established according to the history of exposure to DMS, symptoms and signs of respiratory mucosal irritation, findings on chest radiographs, and abnormalities of leukocyte count. Emergency treatment included prophylactic use of glucocorticoids, supplemental oxygen, sedatives, and antibiotics for prevention and treatment of laryngeal and pulmonary edema, pulmonary infections, and other complications. Follow-up studies for 2-12 years have found only mild to moderate impairment in ventilatory capacity in eight cases, with no abnormal findings in ECG, chest films, and routine blood tests. Nearly all patients have resumed their usual work.     

Methanol-mediated,modular self-assembly of antiparallel β-dimers

The backbone-modified tripeptide Bz-Aib-NHCOCO-Aib-OMe ( l ), in which the central Cα has been replaced with CO, self-assembles in the solid state into highly ordered two-dimensional arrays through MeOH mediated intermolecular stacking of dimeric ‘disk’ modules formed by an antiparallel β-sheet-type arrangement of tripeptide molecules. The Cα(C′O)N(C′O) (C′O)NC^α segment is nearly coplanar (average deviation from a mean least-square plane is ± 0.037 Å). The oxalyl moiety forms two pseudo-C₅ intramolecular hydrogen bonds. Crystal parameters are as follows: C₁₈H₂₃N₃O⁶CH₃OH, triclinic space group P1 a = 9.796(4), b = 10.348(3), c = 11.836(4) Å, α= 78.28(3), β= 73.72(3), γ= 69.45(3), R = 0.082 for 1747 reflections measured with ‖Fo‖3σ(F).     

NMR studies on the structure of some cyclic and linear antagonists of luteinizing hormone-releasing hormone (LHRH)

The structure of cyclic antagonists of luteinizing hormone-releasing hormone (LHRH), Ac-D-Phe(p-Cl)¹-D-Phe(p-C1)²-Trp³-Ser⁴-c(Asp⁵-D-Arg⁶-Leu⁷-Lys⁸)-Pro⁹-D-Ala¹⁰-NH₂ ( I ), Ac-D-Phe(p-Cl⁾l-D-Phe(p-Cl)²-D-Trp³-Ser⁴-c(Glu⁵-Arg⁶-Leu⁷-Lys⁸)-Pro⁹-D-Ala¹⁰-NH₂ ( II ) and their linear analogues, Ac-D-Phe(p-Cl)¹-Phe(p-C1)²-Trp³-Ser⁴-Asp⁵-D-Arg⁶-Leu⁷-Lys⁸-Pro⁹-D-Ala¹⁰-NH₂ ( III ) and Ac-D-Phe(p-Cl)¹-D-Phe(p-C1)²-Trp³-Ser⁴-Glu⁵-D-Arg⁶-Leu⁷-Lys⁸-Pro⁹-D-Ala¹⁰-NH₂ ( IV ), have been studied by NMR spectroscopy. The cyclic peptides I and II are more potent antagonists than the corresponding linear peptides in an in vivo assay. All the peptides show propensity of an unusual type II′β-turn involving residues 3–6. Cyclic analogues also show some additional structure around residues 7 and 8 which is absent in the linear peptides. This additional structure in the cyclic peptides may be due to a minor conformation with a β-turn between residues 5 and 8. © Munksgaurd 1995.     

过氧化氢诱导鼠晶状体上皮细胞凋亡中 Caspase-2的表达及意义

目的探讨过氧化氢诱导鼠白内障形成过程中晶体上皮凋亡细胞中半胱氨酸天冬氨酸酶-2(Cas-pase-2)的表达及意义。方法大鼠晶状体器官离体培养后，用免疫组织化学方法检测晶体上皮细胞Caspase-2的表达。结果随过氧化氢损伤时间的处长，晶体上皮细胞Caspase-2的表达逐渐增强，与晶体混浊程度正相关。结论过氧化氢可以诱导鼠晶体上皮细胞Caspase-2的表达，后者可能参与晶体上皮细胞凋亡和白内障的形成。