Direct Solid-Phase Synthesis of the β-Amyloid (1-42) Peptide Using Controlled Microwave Heating

被引:62
作者
Bacsa, Bernadett [1 ,2 ,3 ]
Bosze, Szilvia [3 ]
Kappe, C. Oliver [1 ,2 ]
机构
[1] Karl Franzens Univ Graz, Christian Doppler Lab Microwave Chem, A-8010 Graz, Austria
[2] Karl Franzens Univ Graz, Inst Chem, A-8010 Graz, Austria
[3] Eotvos Lorand Univ, Hungarian Acad Sci, Res Grp Peptide Chem, H-1117 Budapest, Hungary
关键词
ALZHEIMERS-DISEASE; EFFICIENT SYNTHESIS; PROTEIN TOXICITY; NEUROTOXICITY; SEQUENCES; PURIFICATION; IRRADIATION; BETA-AMYLOID(1-43); PATHOGENESIS; RACEMIZATION;
D O I
10.1021/jo100136r
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Standard linear Fmoc/t-Bu solid-phase synthesis of the 42-mer beta-amyloid (1-42) peptide was achieved under controlled microwave conditions at 86 degrees C using inexpensive DIC/HOBt as coupling reagent on ChemMatrix resin. In order to avoid racemization of the sensitive amino acids, the coupling of the three His residues in the difficult peptide sequence was performed at room temperature. The desired peptide was obtained within 15 h overall processing time in high yield and purity (78% crude yield).
引用
收藏
页码:2103 / 2106
页数:4
相关论文
共 49 条
[31]   Efficient synthesis of a β-peptide combinatorial library with microwave irradiation [J].
Murray, JK ;
Farooqi, B ;
Sadowsky, JD ;
Scalf, M ;
Freund, WA ;
Smith, LM ;
Chen, JD ;
Gellman, SH .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (38) :13271-13280
[32]   Application of microwave irradiation to the synthesis of 14-helical β-peptides [J].
Murray, JK ;
Gellman, SH .
ORGANIC LETTERS, 2005, 7 (08) :1517-1520
[33]   Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis [J].
Palasek, Stacey A. ;
Cox, Zachary J. ;
Collins, Jonathan M. .
JOURNAL OF PEPTIDE SCIENCE, 2007, 13 (03) :143-148
[34]   IMPROVED PREPARATION OF BETA-AMYLOID(1-43) - STRUCTURAL INSIGHT LEADING TO OPTIMIZED POSITIONING OF N-(2-HYDROXY-4-METHOXYBENZYL) (HMB) BACKBONE AMIDE PROTECTION [J].
QUIBELL, M ;
TURNELL, WG ;
JOHNSON, T .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1995, (16) :2019-2024
[35]   PREPARATION AND PURIFICATION OF BETA-AMYLOID(1-43) VIA SOLUBLE, AMIDE BACKBONE PROTECTED INTERMEDIATES [J].
QUIBELL, M ;
TURNELL, WG ;
JOHNSON, T .
JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (07) :1745-1750
[36]   A convenient microwave-enhanced solid-phase synthesis of difficult peptide sequences: Case study of Gramicidin A and CSF114(Glc) [J].
Rizzolo, Fabio ;
Sabatino, Giuseppina ;
Chelli, Mario ;
Rovero, Paolo ;
Papini, Anna Maria .
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, 2007, 13 (1-2) :203-208
[37]   INTRACEREBRAL BETA-AMYLOID(25-35) PRODUCES TISSUE-DAMAGE - IS IT NEUROTOXIC [J].
RUSH, DK ;
ASCHMIES, S ;
MERRIMAN, MC .
NEUROBIOLOGY OF AGING, 1992, 13 (05) :591-594
[38]  
Sabatino G, 2008, CURR OPIN DRUG DISC, V11, P762
[39]   THE MOLECULAR PATHOLOGY OF ALZHEIMERS-DISEASE [J].
SELKOE, DJ .
NEURON, 1991, 6 (04) :487-498
[40]   PHYSIOLOGICAL PRODUCTION OF THE BETA-AMYLOID PROTEIN AND THE MECHANISM OF ALZHEIMERS-DISEASE [J].
SELKOE, DJ .
TRENDS IN NEUROSCIENCES, 1993, 16 (10) :403-409