共查询到20条相似文献,搜索用时 46 毫秒
1.
本文介绍了高活力、长效和速效胰岛素类似物的研究进展,包括它们的分子特点,生物活性,并讨论了高生物活力,长效和速效的可能分子基础,以及它们在临床上应用的前途。 相似文献
2.
以工程化制备由分子内在因素制导的可溶性长效胰岛素为目标,提出以“增加次级键,稳化寡聚体”原理,用以减缓注射进入体内的胰岛素六聚体的解聚速率,形成能持续供应胰岛素单体的“库”,从而获得长效作用。据此以精确的胰岛素三维结构为基础,进行了分子设计和计算机模拟,提出了对胰岛素的B链c端和N端修饰产生长效性的分子改造方案,重点分析了B2Lys/Arg和B31Lys/Arg胰岛素。用化学半合成制备的上列二种胰岛素,生物学测试表明确有长效性。2埃分辨率B31-Arg人胰岛素晶体结构的测定显示了Arg-B31与相邻分子Glu-B21间存在一对附加氢键作为长效效应的主要结构基础,证实分子设计思想的基本正确性。 相似文献
3.
以去B链C端八肽胰岛素和化学合成的IGF-I的22-29及22-32为底物,用酶促半合成方法制备了杂交分子“胰岛素-类胰岛素茵子-I”,Ins/IGF-I和Ins-IGF-I。研究了它们的胰岛中生物活性。结果表明,猪胰岛素B链C端B27的Thr被Asn取代,B30的Ala被Ala被Thr取代同时B25-B26及B28-B29氨基酸顺序颠紧及在B链C末端延长3肽都不影响胰岛素的生物活力。 相似文献
4.
以去B链C端八肽胰岛素(DOI)和化学合成的IGF-I的22~29(8肽)及22-32(11肽)为底物,用酶促半合成方法制备了杂交分子“胰岛素-类胰岛素生长因子-I,Ins/IGF-I(8)和Ins/IGF-I(11)。研究了它们的胰岛素生物活性,结果表明,猪胰岛素B链C端B27的Thr被Asn取代,B30的Ala被Thr取代同时B25~B26及B28-B2k9氨基酸顺序颠倒以及在B链C末端延长3肽(Gly-Tyr-Gly)都不影响胰岛素的生物活力。 相似文献
5.
“胰岛素-类胰岛素生长因子-Ⅰ片段”杂交分子的促生长活性研究张新,唐月华,冯佑民,景乃禾(中国科学院上海生物化学研究所,中国科学院上海生物化学研究所分子生物学国家重点实验室,200031)关键词胰岛素,类胰岛素生长因子-Ⅰ,杂交分子,促生长活性胰岛素... 相似文献
6.
[B3-Lys]-胰岛素的研究:受体结合及生物活性 总被引:3,自引:0,他引:3
本文用125T-[B3-Lys]-胰岛素和125Ⅰ-胰岛素研究了[B3-Lys]-胰岛素和胰岛素与人胎盘细胞膜(HPM)胰岛素受体结合特性并进行了比较。实验结果表明[B3-Lys]-胰岛素与EPM胰岛素受体结合能力比天然猪胰岛素高。由竞争取代曲线得到的[B3-Lys]-胰岛素和猪胰岛素的IC(50)值分别为0.65和1.11nmol/L。经Scatchard分析得出[B3-Lys]-胰岛素与HPM胰岛素受体中高亲和位点和低亲和位点结合的亲和常数分别为1.72×109和2.27×106L/mol,而猪胰岛素分别为1.26×109和1.47×106/mol。促脂肪细胞合成脂肪实验结果表明[B3-Lys]-胰岛素也同样具有比天然猪胰岛素更高的离体生物活力,EC(50)分别为0.175和0.301nmol/L。可见[B3-Lys]-胰岛素的受体结合能力和高体生物活力都为猪胰岛素的1.7倍。 相似文献
7.
在胰岛素结构模体n1-Cys-Gly-X10-Cys-n2-Cys-Cys-X3-Cys-X8-Cys-n3中,有7个绝对保守的氨基酸残基,只有位于B8位的是Gly。通过定点突变将其改变为Ala,得到「B8Ala」人胰岛素,其受体结合能力和体内生物活力分别为天然猪胰岛素的2.5%和10%。「B8Ala」人胰岛素和重组人胰岛素的远紫外圆二色谱比较表明,「B8Ala」人胰岛素的α-螺旋的相对含量有一家 相似文献
8.
本文报道了胰岛素分子中B1 ̄3序列(Phe-Val-Asn)为Ala-Ala-Lys取代的胰岛素类似物制备及其生物性质。[B1Ala,B2Ala,B3Lys]-胰岛素仍保留天然胰岛素的全部体内活性和受体结合能力,但体外促脂肪生成活性和免疫活性分别只为胰岛素的70%和0.88%。本文还就胰岛素B链N端肽段对其结构和功能的影响进行了讨论。 相似文献
9.
胰岛素蛋白质工程研究进展 总被引:1,自引:0,他引:1
近年来,胰岛素蛋白质工程研究进展很快,主要介绍具有临床意义的速效长效和高效胰岛素研究概况,包括分子设计基础,生物活性和应用前景等.此外,还讨论了胰岛素的受体结合部位及胰岛素与其受体相互作用的研究近况. 相似文献
10.
高稳定人胰岛素的晶体学研究:Ⅲ,A21-Asp突变体的结晶和初步晶体学分析 总被引:2,自引:2,他引:0
研究一系列有明确意义改性胰岛素的结构将有益于新型胰岛素分子的设计。经蛋白质工程制备的AspA21—人胰岛素(ADHI)基本保持了生物活力,而在酸性溶夜(pH3—4)中的稳定性比天然胰岛素在中性溶液中高5—10倍。本文报道ADHI的结晶、初步晶体学研究及中等分辨率衍射数据的收集。ADHI晶体属R3空间群:a_H=b_H=82.72埃,c_H=34.02埃。 相似文献
11.
12.
13.
Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis
It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis. 相似文献
14.
15.
16.
17.
RICHARD E. NORRIS 《Botanical journal of the Linnean Society. Linnean Society of London》1991,106(1):1-40
Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera. 相似文献
18.
JOAN VALUÈS MONTSERRAT TORRELL NÚRIA GARCIA JACAS 《Botanical journal of the Linnean Society. Linnean Society of London》2001,137(4):399-407
Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted. 相似文献
19.
肝癌中HBV和HCV基因和抗原的分布及意义 总被引:1,自引:0,他引:1
采用原位分子杂交方法检测HCV
RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV
RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV
RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV
X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV
C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细 相似文献
20.
H.-R. GREGORIUS 《Biological journal of the Linnean Society. Linnean Society of London》1984,23(2-3):157-165
For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment. 相似文献
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment. 相似文献