Science：可以侦测膜下蛋白的小分子探针

生物谷

镶嵌在细胞膜上的蛋白质，参与着非常重要的细胞生理反应，就目前药物研发的对象而言，几乎有近三分之二的药物标的，是位于细胞膜上的蛋白质，而就相关的研究数据显示，位居细胞膜下镶嵌着的膜下蛋白，扮演着同样相同的重要角色，不过却因为缺乏着适当的工具，使得探索膜下蛋白的过程，受到了相当程度的阻碍。

这次宾州大学医学院的科学家，以血液凝结的过程为目标，锁定了称为的 integrinsIIb3、 integrinsV3蛋白质，利用蛋白质序列与结构的数据，透过计算机算法的辅助，设计出可以黏着特定膜下蛋白区域的小分子探针 (probes)，据了解血小板上的 integrins蛋白质，和血液的凝结过程中扮演着关键的重要角色。

目前就研究数据看来，这一个新的探针工具，可以成功的以插入的方式，找到血小板 (platelets)下的 integrins分子，而就这样的一个标示动作来说，科学家可以说找到了一个有效的工具，可以切入膜下蛋白质的研究窗口。

(资料来源 : Bio.com)

原始出处: http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=27600001

部分英文原文：

Science 30 March 2007:
Vol. 315. no. 5820, pp. 1817 - 1822
DOI: 10.1126/science.1136782

Research Articles

Computational Design of Peptides That Target Transmembrane Helices

Hang Yin,1* Joanna S. Slusky,1* Bryan W. Berger,1 Robin S. Walters,1 Gaston Vilaire,2 Rustem I. Litvinov,3 James D. Lear,1 Gregory A. Caputo,1 Joel S. Bennett,2 William F. DeGrado1,4 ${dagger}$

A variety of methods exist for the design or selection of antibodies and other proteins that recognize the water-soluble regions of proteins; however, companion methods for targeting transmembrane (TM) regions are not available. Here, we describe a method for the computational design of peptides that target TM helices in a sequence-specific manner. To illustrate the method, peptides were designed that specifically recognize the TM helices of two closely related integrins ( ${alpha}$ IIbß3 and ${alpha}$ vß3) in micelles, bacterial membranes, and mammalian cells. These data show that sequence-specific recognition of helices in TM proteins can be achieved through optimization of the geometric complementarity of the target-host complex.

1 Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Hematology-Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

${dagger}$ To whom correspondence should be addressed. E-mail: wdegrado@mail.med.upenn.edu