鑲嵌在細(xì)胞膜上的蛋白質(zhì),，參與著非常重要的細(xì)胞生理反應(yīng),，就目前藥物研發(fā)的對(duì)象而言，幾乎有近三分之二的藥物標(biāo)的,，是位于細(xì)胞膜上的蛋白質(zhì),，而就相關(guān)的研究數(shù)據(jù)顯示，位居細(xì)胞膜下鑲嵌著的膜下蛋白,，扮演著同樣相同的重要角色,，不過(guò)卻因?yàn)槿狈χm當(dāng)?shù)墓ぞ?，使得探索膜下蛋白的過(guò)程,，受到了相當(dāng)程度的阻礙。
這次賓州大學(xué)醫(yī)學(xué)院的科學(xué)家,，以血液凝結(jié)的過(guò)程為目標(biāo),，鎖定了稱(chēng)為的 integrinsIIb3、 integrinsV3蛋白質(zhì),，利用蛋白質(zhì)序列與結(jié)構(gòu)的數(shù)據(jù),，透過(guò)計(jì)算機(jī)算法的輔助，設(shè)計(jì)出可以黏著特定膜下蛋白區(qū)域的小分子探針 (probes),，據(jù)了解血小板上的 integrins蛋白質(zhì),，和血液的凝結(jié)過(guò)程中 扮演著關(guān)鍵的重要角色。
目前就研究數(shù)據(jù)看來(lái),，這一個(gè)新的探針工具,，可以成功的以插入的方式，找到血小板 (platelets)下的 integrins分子,，而就這樣的一個(gè)標(biāo)示動(dòng)作來(lái)說(shuō),，科學(xué)家可以說(shuō)找到了一個(gè)有效的工具，可以切入膜下蛋白質(zhì)的研究窗口,。
(資料來(lái)源 : Bio.com)
原始出處: 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
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 (IIbß3 and 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.
To whom correspondence should be addressed. E-mail: [email protected]
