Liver411:分子楔可以导致病毒组装失败

特深沉

原文由liver411发表于英文版

Molecular wedge could lead normal virus formation astray
InfoTrac Web: InfoTrac OneFile.

Source: Virus Weekly, June 18, 2002 p3.

Title: Molecular wedge could lead normal virus formation astray in
hepatitis B.(Brief Article)

Subjects: Hepatitis B - Development and progression
Locations: United States
SIC code: 8730

Electronic Collection: A87152119
RN: A87152119
Full Text COPYRIGHT 2002 NewsRX
2002 JUN 18 - (NewsRx.com & NewsRx.net) -- by Sonia Nichols, senior medical
writer - Small molecules that act like secret agents could be key to
disrupting the formation of hepatitis B and other viruses, suggest research
ers at the University of Oklahoma.

2002 JUN 18 - (NewsRx.com & NewsRx.net) （Sonia Nichols，资深医学作家）
Oklahoma 大学的研究人员提出，小分子可以象特工一样，破坏HBV或其他病毒的形成。

The scientists think a molecule known as bis-ANS and others like it could form the underpinnings for new types of antiviral agents in the future.

科学家认为，一种名为bis-ANS的小分子和其类似物在未来可能成为新类型抗病毒药物
的基础。

Explaining that HBV capsids can be produced in the lab, Adam Zlotnick and
colleagues at the University of Oklahoma Health Sciences Center recently
described in the Journal of Virology how bis-ANS acts as a wedge to disrupt
capsid assembly. After binding to capsid building blocks, the molecule,
Which inactivates mechanisms resembling enzymes, works slyly to form
nonse-type polymers instead of a capsid.

Oklahoma俄克拉荷马大学健康科学中心的Adam Zlotnick及其同事解释说，HBV外壳可
以在实验室制造。在最近的Virology期刊上，他们描述bis-ANS象楔子一样破坏了
HBV外壳的组装。该分子与外壳结构模块结合以后，阻止了组装酶的活动，巧妙地形成
了没有意义的聚合体，而不是HBV外壳。

"Using equilibrium dialysis to investigate binding of bis-ANS to free capsid
protein, we found that only one bis-ANS molecule binds per capsid protein
dimer, with an association energy of -28 [plus-or-minus sign] 2.0 kJ/mol,"
Zlotnick and coauthors noted.

Zlotnick及合作者说，“通过平衡分离法调查bis-ANS同自由HBV外壳分子的结合情
况后，我们发现每个外壳蛋白只结合了一个bis-ANS分子，结合能是
-28±2.0千焦/摩尔”

Chromatographic analysis indicated that bis-ANS used ionic strength to disrupt particle assembly, and its binding energy was almost equivalent to that reportedly demonstrated in unassembled protein, according to Zlotnick and colleagues (A small molecule inhibits and misdirects assembly of hepatitis B virus capsids, J Virol, 2002;76(10):4848-4854).

色谱分析显示，bis-ANS通过离子强度破坏HBV颗粒的组合，它的结合能几乎与未组合
的蛋白分子相等。（参见A small molecule inhibits and misdirects assembly of
hepatitis B virus capsids, J Virol, 2002;76(10):4848-4854）.

"The data indicate that capsid protein bound to bis-ANS did not participate in assembly; this mechanism of assembly inhibition is analogous to competitive or noncompetitive inhibition of enzymes," the investigators pointed out.

“该数据显示，外壳蛋白与bis-ANS结合后不参与组装，这种抑制组合的机制类似于
对酶的竞争性或非竞争性抑制。”

Instead of allowing normal capsid formation, bis-ANS caused aberrant,
noncapsid polymers to form during the dialysis experiments.

在透析实验中，bis-ANS分子导致了异常的，不能组装的聚合体，代替了正常的外壳构
成。

"We propose that bis-ANS acts as a molecular "wedge" that interferes with
normal capsid protein geometry and capsid formation; such wedges may represent a new class of antiviral agent," Zlotnick and colleagues proposed.

“我们认为，bis-ANS象一个分子‘楔’，干扰了正常外壳蛋白的空间结构和外壳的
形成；这种楔子可能形成新的一个抗病毒药物家族。



作者通讯处：
The corresponding author for this study is Adam Zlotnick, P.O.B. 26901, BRC
464, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. E-mail: [email protected].

Key points reported in this study include:
该项研究的关键点包括：

* A small molecule known as bis-ANS binds to capsid protein in HBV and is able to disrupt normal capsid assembly
名为bis-ANS的小分子与HBV外壳蛋白结合，可以破坏正常外壳的组装。
* Bis-ANS causes the formation of aberrant, noncapsid polymers
bis-ANS导致异常的构造，无法组装的聚合物。
* Molecules like bis-ANS act like a wedge to disrupt normal capsid
construction, and could potentially be used in the clinical setting as
antivirals
bis-ANS类的分子象楔子一样破坏正常的外壳结构，有希望在临床上用于抗病毒。


This article was prepared by Virus Weekly editors from staff and other
reports.

-- End --

[此贴子已经被特深沉于2002-10-31 0:24:54编辑过]

特深沉

我觉得bis-ANS中的ANS即为ANTI-SENSE 的缩写。不知对否。


我在‘科学美国人’网站上，看过‘killing the messenger’.在文后，有一段话是用RNAi同ANTI-SENSE
比较。据称RNAi（RNA干涉）比ANTI-SENSE有更高的期望值。问题是这种小分子没有选择性，
进入人体后可能同其他蛋白分子结合而失效，或带来副作用。

特深沉

以下节选自‘killing the messenger’


Brenda L. Bass, a Howard Hughes Medical Institute investigator at the
University of Utah, comments that RNAi has been shown so far in laboratory
experiments to be more efficient at stifling gene expression than another
technique called antisense RNA. Several antisense drugs, which also
function by binding to mRNA, are now in human tests, but their mechanism
of action is still poorly understood, and they are somewhat fickle. "With
antisense, you don't know if it will work on your given gene," Bass says.
"It is clear that RNAi is much, much more effective."

Brenda L. Bass（Howard Hughes Medical Institute investigator at the University of Utah），认为
RNAi在实验室中表现出了更高的效能（比起另外的称作antisense RNA的药物）。很多
antisense RNA药物（它们也是与mRNA结合），正在作人体实验，但它们的行为机制仍不明确，
它们的表现变幻无常。Bass 说，“利用antisense 时，你不能确定她是否能作用于特定的基
因。很明显，RNAi更加有效。”

特深沉

以下是‘killing the messenger’ 一文后的参考。


GETTING INTO THE GROOVE
Another method for shutting down genes is to bypass the messenger
and go straight to the source: the DNA helix. Michael J. Hannon
of the University of Warwick in England and his co-workers have
devised synthetic molecular cylinders that can bind to the major
groove formed by the twisting of the DNA helix. The cylinders bend
the DNA so that its genes are inaccessible to the enzymes that
normally convert the genetic instructions to mRNA.
But so far the process is nonspecific: the scientists have yet
to figure
out how to target particular genes for shutdown.
关闭基因的另一种方法是旁路信使，直捣源头：DNA螺旋。Michael J. Hannon （of
the University of Warwick in England ）发明了人工合成圆柱分子，它可以结合DNA
螺旋形成的凹槽。圆柱分子嵌进DNA后，它的基因不能接近酶，正是这种酶使基因
转换出mRNA。但这个过程是非特异的：科学家迄今还不知道怎样瞄准关闭特定
的基因。

ILOVELIVER

可能RNAi更有希望。近年来，抗病毒方法的机理研究有突破。

liver411

Thanks for your effort and help.

咪咪

不知道这些新技术什么时候可以用于临床，我盼呀盼呀！
希望那一天早点来！

sunday

对于什么东西都不要希望值太高

特深沉

UP