氨基糖酸在药物分子设计与合成中的应用

用非天然的分子实体模拟天然活性分子以提高药物的活性和稳定性.是药物化学中的一个研究热点。氨基糖酸综合了糖和氨基酸结构特征和化学反应特性.是一类新型非天然的多肽模拟物构建模块,广泛的应用在多肽模拟学、组合化学和人工受体分子的构建中。本文综述了近年来氨基糖酸在药物分子设计与合成中的应用进展。     

MALDI-TOF质谱技术研究海兔神经连索外表层的多肽组成

厦门蓝斑背肛海兔(Notarcusleachiicirrosus)中枢神经系统(CentralNervousSystem,CNS)缺少腹神经节。杂斑海兔(AplysiajulianaQuoy &Gaimard)和美国加州海兔(Aplysiacalifornia)的CNS均有腹神经节。生物质谱技术研究表明 ,美国加州海兔和厦门蓝斑背肛海兔的CNS的神经连索外表层含有丰富的多肽组成 ,部分多肽表现出转移特性。     

管藻目绿藻刺松藻(Codium fragile)PSI色素蛋白复合物结构及多肽组成

采用温和的聚丙烯酰胺凝胶电泳（PAGE）法，从管藻目录藻刺松藻中分离到不同解离程度的光系统I（PSI）复合物，以及核心复合物CCI、捕光复合物LHCI和LHCI的亚组分，并就其多肽组成及相互关系做了研究。纯化的CCI复合物只含有66和56kDa多肽，荧光发射主峰在714－715nm；LHCI的77K荧光峰在683－684nm，没有高等植物730nm特征荧光，含有PSI复合物中的全部4种24.7-27.5kDa多肽。将中心复合物CPI再电泳，得到了只含24．5和27．2kDa多肽的LHCI亚组分。从而证实刺松藻LHCI也可分裂为含有光合色素的两个部分，它们与CCI结合的紧密程度不同。     

A polypeptide from Chlamys farreri inhibits UVB-induced HaCaT cells apoptosis via the Apaf-1/caspase-9 and Smac/XIAP signaling pathway

A novel marine active polypeptide(PCF),isolated from the gonochoric Chinese scallop,Chlamys farreri,has potential antioxidant and anti-apoptotic activity against ultraviolet irradiation.We investigated whether UVB-induced HaCaT cell apoptosis occurs via the mitochondrial pathways Apaf-1/caspase-9 and Smac/XIAP/caspase-3.We then investigated the molecular mechanisms controlling the anti-apoptotic effect of PCF.Pre-treatment with PCF and caspase-9 inhibitor significantly inhibited UVB-induced apoptosis in HaC...     

Polypeptide from Chlamys farreri inhibits UVB-induced apoptosis of HaCaT cells via iNOS/NO and HSP90

Polypeptide from Chlamys farreri(PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri,and was found to be an effective antioxidant in our recent studies.In this study,we investigated the effect of PCF on ultraviolet B(UVB)-induced apoptosis of HaCaT cells and the intracellular signaling pathways involved.Pretreatment with the inducible nitric oxide synthase(iNOS) inhibitor S-methylisothiourea sulfate inhibited UVB-induced apoptosis,indicating that iN...     

酶解蓝圆鲹鱼肉蛋白制备小分子肽的工艺研究

以蓝圆鲹为原料,酶解蓝圆鲹鱼肉蛋白制备小分子肽。运用响应面试验设计优化蓝圆鲹蛋白酶解的工艺条件,探讨了酶种类和添加量、液固比、酶解温度、酶解时间对多肽提取率的影响。结果表明:选用木瓜蛋白酶,添加量为0.10%,液固比2∶1,酶解温度54.4℃,酶解时间3.18 h下,多肽提取率为32.35%。     

Effects of polypeptide from<Emphasis Type="Italic">Chlamys farreri</Emphasis> on amino acid content in guinea pig skin irradiated by chronic ultraviolet A and B

We examined the effects of polypeptide fromChlamys farreri (PCF) on the amount of hydroxyproline in guinea pig skin irradiated by chronic ultraviolet A (UVA) and ultraviolet B (UVB) radiation. PCF was applied locally before repeated exposure of guinea pig to UVA and UVB. The contents of hydroxyproline and other amino acids in guinea pig skin were determined by automatic amino acid analyzer. Our results showed that: (1) long-time UVA and UVB radiation can reduce dramatically the amounts of hydroxyproline, aspartic acid, threonine, glycine, phenylalanine and lysine in guinea pig skin in comparison with the control group (P<0.05); (2) Compared with model group, pre-treatment with 5% and 20% PCF prior to UVA and UVB radiation can inhibit the decline of amino acids content in guinea pig skin in a dose-dependent manner (P<0.05). As the decrease of hydroxyproline, glycine and lysine contents in the skin directly reflexes type I collagen degeneration, our results indicated that the chronic application of PCF can protect skin type I collagen against UV radiation, and thus protect skin from photoaging. Project No. 39970638 supported by the NSFC, and also supported by the Science and Technology Bureau of Qingdao (No: 2001-28-50).     

罗非鱼鱼皮肽的体外ACE抑制活性、消化性及分子对接对比

【目的】分析罗非鱼鱼皮多肽LSGYGP的ACE抑制活性、胃肠道消化稳定性以及与降压药卡托普利在分子对接的对比。【方法】用HHL法测定多肽的IC50值和抑制模式,测定多肽在模拟胃肠道消化中的稳定性,MTT法检测细胞活力,Western blot法检测诱导型一氧化氮合酶(i NOS)、环氧合酶-2(COX-2)、内皮素-1(ET-1)等蛋白表达情况,将多肽、卡托普利分别与ACE进行分子对接对比分析。【结果】LSGYGP的半抑制率(IC50)值为2.57μmol/L,表现为混合非竞争性抑制,4 h内模拟胃肠道消化较为稳定;MTT法验证多肽LSGYGP对HUVEC细胞无毒性作用(P 0.05),且能明显提高Ang Ⅱ诱导组的HUVEC细胞活力(P 0.01);与对照组相比,随实验组多肽浓度增加,i NOS、COX-2和ET-1的表达明显逐渐减少(P0.001)。对接结果表明,氢键是LSGYGP与ACE结合结构中的支撑力,而卡托普利通常与ACE的Zn~(2+)离子形成紧密结合的相互作用。【结论】消化稳定的罗非鱼鱼皮多肽可明显抑制血管收缩因子和炎症因子的表达,展现了较好ACE抑制活性,LSGYGP与卡托普利的活性差异可能是由于ACE分子对接的作用力不同,这些可作为研发少副作用ACE抑制剂的药理基础。     

The polypeptide in Chlamys farreri can protect human dermal fibroblasts from ultraviolet B damage

~~The Polypeptide in Chlamys farreri can protect human dermal fibroblasts from ultraviolet B damage@张玉江$Qingdao University, Medical College,Qingdao Shandong 266021,China @战松梅$Qingdao University, Medical College,Qingdao Shandong 266021,China @曹鹏利$Qingdao University, Medical College,Qingdao Shandong 266021,China @刘宁$Qingdao University, Medical College,Qingdao Shandong 266021,China @陈雪红$Qingdao University, Medical College,Qingdao Shandong 266021,China @…     

Protective Effect of Topically Applied Polypeptide from Chlamys farreri Against Ultraviolet Radiation-Induced Chronic Skin Damage in Guinea Pig

INTRODUCTIONSolarultraviolet(UV)radiationisknowntobeamajoretiologicalriskofphotoaging.AsUVC(2 0 0nm -2 90nm)isabsorbedentirelybythestratosphericozonelayer,sunlightontheearthsur faceiscomposedofUVA (3 2 0nm -4 0 0nm)andUVB (2 90nm -3 2 0nm)only.UVAradiationenergyaccountsformorethan 90 %ofsolarUV ;andpenetratesthebasallayerofepidermismoreefficientlythanUVB (Brulsetal.,1984) .However,atsimilardosages,UVBismuchmoremuta genicthanUVA (Drobetskyetal.,1995) .Furthermore ,humanskinisexp…