鹿茸多肽的抗炎作用

鹿茸多肽(Pilose antler peptide,PAP)10和20mg·kg~(-1)ip对各种急慢性炎症具有明显的抑制作用。PAP可使大鼠肾上腺中的抗坏血酸和胆固醇含量降低,并使血清皮质醇含量明显升高;用地塞米松阻断垂体后,上述作用仍然存在。于去肾上腺大鼠PAP仍不失其抗炎作用。可见,PAP的抗炎作用不完全依赖于垂体—肾上腺皮质系统。     

利用人源Caco-2细胞单层模型研究罂粟碱、N-甲基四氢罂粟碱和头花千金藤碱在人肠道的吸收

研究罂粟碱(papaverine，PAP)、N-甲基四氢罂粟碱(laudanosine，LAU)和头花千金藤碱(cepharanthine，CEP)在人小肠的吸收。利用人源结肠腺癌细胞系Caco-2细胞单层模型研究PAP、LAU和CEP由绒毛面(AP侧)到基底面(BL侧)、BL侧到AP侧两个方向的转运过程。应用HPLC-UV对上述3个生物碱进行定量分析，计算转运参数和表观渗透系数，并与易吸收性对照药普萘洛尔和难吸收性对照药阿替洛尔进行比较。PAP、LAU和CEP由AP侧到BL侧的表观渗透系数(P_app)分别为(3.524±0.223)×10^-5、(2.821±0.050)×10^-5和(6.524±0.052)×10^-5 cm·s^-1；由BL侧到AP侧的P_app分别为(5.095±0.508)×10^-5、(2.646±0.146)×10^-5和(5.495±0.036)×10^-5 cm·s^-1，与在Caco-2细胞单层模型上呈良好吸收的阳性对照药普萘洛尔基本一致。PAP、LAU和CEP的P_{app A→B}/P_{app B→A}分别为0.69、1.07和1.19；PAP外流是摄取的1.45倍。PAP、LAU和CEP可以通过小肠上皮细胞被动吸收进入体内，属于良好吸收的药物。在三者的吸收转运过程中，油/水分配系数起着关键性的作用。PAP在Caco-2细胞单层模型中的转运可能存在外流机制。     

银柴胡环肽类研究

从银柴胡(Stellaria dichotoma L.var lanceolata Bge.)的根中首次分离得到1新化合物,经理化常数,氨基酸组成及光谱分析确定为环六肽结构,命名为银柴胡环肽(stellaria cyclopeptide)。     

胰泌素的放射性碘标记和纯化

胰泌素(Secretin)是由27个氨基酸组成的多肽,与胰高糖素、肠抑胃肽和血管活性肠肽的氨基酸组成有很多相似部分,是调节人体消化系统活动,促进胰液和胰酶分泌的一个重要胃肠多肽激素。应用放射免疫方法测定人体血浆、组织液和组织中的     

马鹿茸促进表皮细胞和软骨细胞分裂的新多肽

目的　研究马鹿(Cervus elaphus Linnaeus)茸多肽的化学结构和促进细胞有丝分裂的生物活性。方法　用酸性水提取鹿茸多肽,多肽组分经过 CM-Sepharose Fast Flow 和 Sephadex G-50 柱色谱分离后,再用反相 HPLC (C₆)纯化。结果　从马鹿茸得到一个单一多肽化合物。结合激光解析电离飞行时间质谱,N-端 Edman 降解和氨基酸分析结果表明,该多肽是由32个氨基酸残基组成的直链多肽,分子量3216u,主要含缬氨酸、丙氨酸、赖氨酸和甘氨酸,无半胱氨酸,其一级结构氨基酸排列顺序为:N端-VLSAADKSNVKAAWGKVGGNAPAFGAEALLRM,与已知蛋白序列同源性远小于 50%。VAPP 促进大鼠表皮细胞(浓度0.4 - 50mg·L^-1)和家兔肋软骨(浓度10 - 50mg·L^-1)细胞增殖。结论　鹿茸多肽是具有促进细胞增殖的新多肽     

环孢素A治疗药物监测研究进展

<正>环孢素A(Cyclosporine A,CsA)是1971年瑞士Sandoz公司从真菌(Tolypocladium Inflatum Gams)分离提取出来的一种由11个氨基酸组成的亲脂性环形多肽。1976年Borel首先报     

肽类药物国内外研究进展

多肽是指由氨基酸组成，氨基酸用肽键连接而成的一类化合物，其在连接方式上与蛋白质相同，通常将少于100个氨基酸组成的称为多肽，而由100个以上氨基酸组成的为蛋白质。但在某些性质方面多肽又有别于蛋白质，如其空间结构较简单、稳定性较高、免疫原性较低或无免疫原性等。所有生物细胞都能合成多肽，同时也受各种多肽的调节。多肽的生物活性广泛而重要，     

鹅绒藤酯Ⅰ的分离和测定

从宁夏产鹅绒藤(Cynanchum chinense R.Br.)地上部分的醇提取物中,分得一新的三萜酯,命名为鹅绒藤酯Ⅰ(cynanester A),经波谱分析和化学反应证明,酯Ⅰ的结构为羽扇醇正己酸酶(l;upeol caproate)。此外还分离鉴定了羽扇醇乙酸酯(lupeol acetate)、正廿四烷酸(lignoceric acid)和β-谷甾醇(β-sitosterol)。     

环孢菌素A的不良反应及防治

环孢菌素A(cyclosporine A,CsA)为11个氨基酸组成的环状多肽,是一种强效的免疫抑制剂,能可逆地特异作用于淋巴细胞.     

补肺活血胶囊联合坎地沙坦酯治疗慢性肺心病的临床研究

目的 探讨补肺活血胶囊联合坎地沙坦酯片治疗慢性肺心病的临床疗效。方法 选取2019年7月—2022年6月在北京市第六医院就诊的110例慢性肺心病患者,按照随机数字表法将所有患者分为对照组和治疗组,每组各55例。对照组患者口服坎地沙坦酯片,1次/d,2片/次。治疗组在对照组基础上口服补肺活血胶囊,4粒/次,3次/d。两组患者连续治疗6个月。观察两组的临床疗效,比较两组患者的水肿、呼吸困难、肺啰音消失时间,以及氧合指数、血氧饱和度、二氧化碳分压、左室射血分数(LVEF)、肺动脉压力(PAP)、三尖瓣反流速度(TR)、N末端B型利钠肽前体(NT-proBNP)、和胎素(CPN)、血管紧张素Ⅱ(Ang Ⅱ)水平。结果 治疗后,治疗组的总有效率(92.73%)明显高于对照组的总有效率(78.18%)(P<0.05)。治疗后,治疗组水肿、呼吸困难、肺啰音消失时间均短于对照组(P<0.05)。治疗后,两组的氧合指数、血氧饱和度显著升高,二氧化碳分压显著降低(P<0.05);治疗组的氧合指数、血氧饱和度高于对照组,二氧化碳分压低于对照组(P<0.05)。治疗后,两组的LVEF明显升高,PAP、TR明显降低(P<0.05);治疗组的LVEF高于对照组,PAP、TR低于对照组(P<0.05)。治疗后,两组的血清NT-proBNP、CPN、Ang Ⅱ水平明显降低(P<0.05),且治疗组血清NT-pro BNP、CPN、AngⅡ水平明显低于对照组(P<0.05)。结论 补肺活血胶囊联合坎地沙坦酯片治疗慢性肺心病的疗效确切,有助于减轻临床症状,改善患者血气指标和心肺功能,减轻心肌损伤。     

Synthesis of the arsenic-containing amino-acids,and their potential applications in peptide chemistry

Trivalent organoarsenic compounds have attracted a great deal of interest because of their potential antineoplastic activities. In this work, we synthesized a series of arsenic-containing amino acid analogues by introducing the structure of 1-arsino-2,6,7-trithiobicyclo[2.2.2]octane to the side chain of modified amino acid derivatives. The protected amino acid (6a) as a typical objective compound was applied in peptide synthesis via the classic procedures for the formation of peptide bond or removal of protecting groups. Our results showed that the application of compound 6a (or 5a) in the peptide chemistry was satisfactory.     

SYNTHESIS OF γ-METHYL-l-LEUCINE (NEOPENTYLGLYCINE,NEO) AND DERIVATIVES SUITABLE FOR PEPTIDE SYNTHESIS

The modified Strecker synthesis of Patel & Worsley was combined with an enzymatic deamidation in the final step, to produce the title compound. The amino acid is a member of the family of the “fat” amino-acids with high lipophilicity and space-filling properties, as estimated by its Hansch hydrophobicity constant and its Charton steric parameter v. It can be used for qualitative and quantitative studies of structure-activity relationships in biologically active peptides. Three of its derivatives suitable for peptide synthesis are also described.     

Design, synthesis, and modeling of novel cyclic thrombin receptor-derived peptide analogues of the Ser42-Phe-Leu-Leu-Arg46 motif sequence with fixed conformations of pharmacophoric groups: importance of a Phe/Arg/NH2 cluster for receptor activation and implications in the design of nonpeptide thrombin receptor mimetics.

The novel cyclic analogues cyclo(Phe-Leu-Leu-Arg-epsilonLys-Dap) (1) and cyclo(D-Phe-Leu-Leu-Arg-epsilonLys-Dap) (2), which differ only in the absolute conformation of Phe, have been designed and synthesized based upon the minimal peptide sequence Phe-Leu-Leu-Arg which has been found to exhibit biological activity for the thrombin receptor. Compound 1, in which all amino acids have the L-configuration, exhibited higher activity in the rat aorta relaxation and rat longitudinal muscle bioassays compared to compound 2, in which the Phe residue is in the D-configuration. This is attributed to the spatial proximity of the Phe and Arg in compound 1 which does not exist in its diastereomeric compound 2, as is depicted from a combination of NMR studies and computational analysis. Structure-activity studies (SAR) showed that the Phe and Arg side chains along with a primary amino group form an active recognition motif that is augmented by the presence of a second primary amino group in the cyclic peptide. We suggest that a comparable cyclic conformation may be responsible for the interaction of linear TRAPs with the thrombin receptor. The validity of this proposition was tested by the synthesis of four active nonpeptide thrombin receptor mimetics. Substance (S)-N-(6-guanidohexanoyl)-N'-(2-amino-3-phenylpropionyl)piperazine (3), in which the pharmacophoric phenyl, guanidino, and amino groups were incorporated onto a piperazine template, was found to be the most active compared to the other synthesized compounds which lack the amino pharmacophoric group.     

A NOVEL SYNTHESIS OF 2-THIOETHER DERIVATIVES OF TRYPTOPHAN

The reaction of L-3a-hydroxy-1,2,3, 3a, 8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (Hpi) with methanethiol, ethanethiol, mercaptoethanol or 3-mercaptopropionic acid in warm aqueous acetic acid gives the corresponding 2-thioether derivatives of tryptophan in 50–80% yield (based on Hpi). Better yields may be obtained in 25% trifluoroacetic acid at room temperature. Cysteine reacts with Hpi to give the double amino acid 2-(L-3-alanylthio)-L-tryptophan (tryptathionine), which is a constituent of the highly poisonous cyclopeptides of Amanita phalloides, such as phalloidin. Reaction of a moderate excess of Hpi with cysteine-SH groups of a tripeptide (glutathione) and a protein (reduced ribonuclease) has also been effected, giving the respective S-tryptophanylated peptide or protein. In both cases, reaction occurred specifically with the -SH groups of cysteine and virtually quantitative covalent binding of tryptophan was verified. The extent of the reaction is easily quantitated by spectrophotometry or by amino acid analysis of the content of oxindolylalanine in the hydrolysate with hot 3-N p-toluenesulfonic acid of the S-tryptophanylated peptide or protein. The reaction should be useful in the field of peptide synthesis, providing a simple method for establishing a cross-link between tryptophan and cysteine, as a basic step in the chemical synthesis of toxic peptides of Amanita phalloides.     

多抗甲素中的氨基酸组分和糖组分分析

本文报道在日立835-50型氨基酸分析仪上,采用两种方法分别对多抗甲素中的氨基酸和糖组分进行定性、定量分折.结果表明在多抗甲素水解产物中,主要成分为甘露糖.多抗甲素系甘露聚糖肽类物质.     

COMPLETE SEQUENCE OF THE GLYCOSYLATED AMINO TERMINAL SEGMENT OF PORCINE PRO-OPIOMELANOCORTIN

The complete sequence of an anterior pituitary glycopeptide corresponding to the first 80 amino acid residues of the amino terminal of pro-opiomelanocortin (POMC) after excision of the signal peptide is reported. This peptide isolated from pig pituitaries shows considerable sequence conservation with its predicted homologues from bovine, murine and human species.     

SEQUENCE OF THE CNBr PEPTIDE CONTAINING THE PUTATIVE ESSENTIAL TYROSINE OF BACILLUS AMYLOLIQUEFACIENS ALPHA AMYLASE*

The amino acid sequence of the cyanogen bromide peptide (peptide B) containing the putative essential tyrosine residue in Bacillus amyloliquefaciens alpha-amylase (EC 3.2.1.1.) was determined. It is composed of 73 amino acids and the “active” tyrosine residue is the N-terminus of the peptide. Upon iodination of the whole enzyme by means of a lactoperoxidase-catalyzed reaction, a minimum of eight tyrosine residues are iodinated. Four of these belong to peptide B. Among the cyanogen bromide peptides, B is the most readily iodinated one. Hence, it is predicted that peptide B is an exposed segment of the amylase molecule.     

Memnopeptide A, a novel terpene peptide from Memnoniella with an activating effect on SERCA2.

The terpene peptide memnopeptide A (1), C76H108N16O18S, MW 1564, was isolated from a culture of the fungus Memnoniella echinata FH 2272 on casein peptone. The structure of the novel compound was elucidated with the aid of 2D NMR experiments and from amino acid analysis and mass spectrometric sequencing of the peptide. The compound consists of a known phenylspirodrimane subunit linked to the decapeptide Met-His-Gln-Pro-His-Gln-Pro-Leu-Pro-Pro. This proline-rich peptide is a subsequence of beta-casein. From the observed absence in the literature of any other highly significant sequence homologues, memnopeptide A can be assumed to arise from metabolic products of the fungus with direct incorporation of constituents of the nutrient medium. The formation of memnopeptide A suggests this may be a mechanism for storage of amines by the fungus. Memnopeptide A has weak antibacterial activity against gram-positive bacteria and effects half-maximal activation of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2) at a concentration of 12.5 microM.     

脱苏氨醇奥曲肽的微波辅助合成

利用自制100 ml微波反应管通过微波辅助固相肽合成技术制得奥曲肽原料药中关键有关物质脱苏氨醇奥曲肽(1)。采用Fmoc策略以2-Cl-Trt-树脂为固相载体,经上载、缩合、脱保护、裂解等操作合成还原型脱苏氨醇奥曲肽,再用空气氧化法并加入活性炭快速氧化得到1,总收率62.9%,单批次产量达3.5 g,中间体及终产物经高分辨质谱及氨基酸分析确证,并通过圆二色谱法研究了环合前后多肽构象的变化。该方法比传统固相合成方法快捷,为研究奥曲肽的关键有关物质提供了可行的合成方法。     

我国氨基酸类药物研究进展

氨基酸是一类具有特殊生理功能的小分子化合物,近年来我国氨基酸类药物发展迅速,总结市场和研究情况,今后小肽、氨基酸螯合物以及氨基酸衍生物可能成为氨基酸类原料药发展的新方向;而复方氨基酸制剂则可能偏重于含谷氨酰胺的营养输液、肠内营养制剂和多腔袋营养制剂的开发。