一項(xiàng)由密西根大學(xué)分析化學(xué)家Kristina Hakansson發(fā)明的一種新技術(shù),，可辨別癌細(xì)胞的多聚糖,，為新的癌癥診斷和治療方法奠定了基礎(chǔ),。
越來越多的證據(jù)顯示,，與癌細(xì)胞表面蛋白連接的多聚糖,，也參與了腫瘤的生長(zhǎng)和擴(kuò)散,。研究人員已經(jīng)鑒定出了這種多聚糖,，但是傳統(tǒng)的分析方法卻不是很有效,。
Hakansson的研究小組證實(shí)，他們的技術(shù)可以用來鑒定多聚糖,，并分析它們的結(jié)構(gòu)特征,。這項(xiàng)研究結(jié)果將刊載于4月15日的Analytical Chemistry上。
通常,，分析化學(xué)的工作人員會(huì)利用質(zhì)譜來分析蛋白質(zhì),。在這個(gè)過程中，蛋白質(zhì)需要進(jìn)入質(zhì)譜儀中,，并通過加熱來將它們變成碎片,。不同片斷的量可以提供與遺傳藍(lán)圖有關(guān)的信息。這也就是所謂的shake-it-til-it-break,。
但是,，如果蛋白質(zhì)上結(jié)合了其它基團(tuán)如磷酸、硫酸或糖,，那么這種鑒定方法就派不上用場(chǎng)了,。為了解決這個(gè)問題，研究人員利用一種叫做電子捕獲裂解（ECD, electron capture dissociation）的方法,，來代替shake-it-til-it-break方法來使蛋白質(zhì)分解,。但是，這種方法需要至少攜帶兩個(gè)正電荷,。
Hakansson的研究組利用金屬如鈣和鐵來攜帶必要的正電荷,。而他們也首次證實(shí)，這種方法可用于選擇性地分解蛋白質(zhì)不同的化學(xué)鍵,，該方法也可以用于測(cè)定含硫酸基團(tuán)蛋白質(zhì),、確定出蛋白質(zhì)上硫酸基團(tuán)的位置。
研究人員表示,，這項(xiàng)工作目前還處于初步階段,，但是他們希望通過測(cè)量特殊的糖分子，研發(fā)出更精密的癌癥診斷工具和治療方法,。
(資料來源 : biocompare)
部分英文原文：
Anal. Chem., 73 (18), 4530 -4536, 2001. 10.1021/ac0103470 S0003-2700(01)00347-X
Web Release Date: August 16, 2001 Copyright © 2001 American Chemical Society
Electron Capture Dissociation and Infrared Multiphoton Dissociation MS/MS of an N-Glycosylated Tryptic Peptide To Yield Complementary Sequence Information
Kristina Håkansson, Helen J. Cooper, Mark R. Emmett, Catherine E. Costello, Alan G. Marshall, and Carol L. Nilsson*
Center for Interdisciplinary Magnetic Resonance, National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive, Tallahassee, Florida 32310, Mass Spectrometry Resource, Boston University School of Medicine, 715 Albany Street R-806, Boston, Massachusetts 02118-2526, and Institute of Medical Biochemistry, Göteborg University, Box 440, SE-405 30 Göteborg, Sweden
Received for review March 23, 2001. Accepted July 2, 2001.
Abstract
Glycoproteins are a functionally important class of biomolecules for which structural elucidation presents a challenge. Fragmentation of N-glycosylated peptides, employing collisionally activated dissociation, typically yields product ions that result from dissociation at glycosidic bonds, with little occurrence of dissociation at peptide backbone sites. We have applied two dissociation techniques, electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD), in a 7-T Fourier transform ion cyclotron resonance mass spectrometer, in the investigation of an N-glycosylated peptide from an unfractionated tryptic digest of the lectin of the coral tree, Erythrina corallodendron. ECD provided c and z ions derived from the peptide backbone, with no observed loss of sugars. Cleavage at 11 of 15 backbone amine bonds was observed. The lack of cleavage at sites located close to the glycosylated asparagine residue may result from steric blocking by the glycan. IRMPD provided abundant fragment ions, primarily through dissociation at glycosidic linkages. The monosaccharide composition and the presence of three glycan branch sites could be determined from the IRMPD fragments. The two types of spectra, obtained with the same instrument, thus provide complementary structural information about the glycopeptide. The current result extends the applicability of ECD for glycopeptide analysis to N-glycosylated peptides and to peptides containing branched, highly substituted glycans.
