An unnatural amino acid that mimics a tripeptide β-strand and forms β-sheetlike hydrogen-bonded dimers

被引:128
作者
Nowick, JS [1 ]
Chung, DM [1 ]
Maitra, K [1 ]
Maitra, S [1 ]
Stigers, KD [1 ]
Sun, Y [1 ]
机构
[1] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA
关键词
D O I
10.1021/ja001142w
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Unnatural amino acid 2 (5-HO2CCONH-2-MeO-C6H3-CONHNH2) duplicates the hydrogen-bonding functionality of one edge of a tripeptide P-strand. It is composed of hydrazine, 5-amino-2-methoxybenzoic acid, and oxalic acid groups and is designated by the three-letter abbreviation "Hao" to reflect these three components. The 2,7-di-tert-butylfluorenylmethyloxycarbonyl (Fmoc*)- and tert-butyloxycarbonyl (Boc)-protected derivatives of Hao are prepared efficiently and in high yield by the condensation of suitably protected derivatives of hydrazine, 5-amino-2-methoxybenzoic acid, and oxalic acid. Fmoc*-Hao and Boc-Hao behave like typical Fmoc- and Boc-protected amino acids and can be incorporated into peptides by standard solid-and solution-phase peptide synthesis techniques using carbodiimide coupling agents. Hao-containing peptide 9 (i-PrCO-Phe-Hao-Val-NHBu) forms a beta-sheetlike hydrogen-bonded dimer in CDCl3 acid CD3OD-CDCl3 solutions. Peptides containing Hao and natural amino acids display hydrogen-bonding surfaces that are complementary to the hydrogen-bonding edges of protein beta-sheets.
引用
收藏
页码:7654 / 7661
页数:8
相关论文
共 56 条
[1]   REGIOSELECTIVE STRUCTURAL AND FUNCTIONAL MIMICRY OF PEPTIDES - DESIGN OF HYDROLYTICALLY-STABLE CYCLIC PEPTIDOMIMETIC INHIBITORS OF HIV-1 PROTEASE [J].
ABBENANTE, G ;
MARCH, DR ;
BERGMAN, DA ;
HUNT, PA ;
GARNHAM, B ;
DANCER, RJ ;
MARTIN, JL ;
FAIRLIE, DP .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (41) :10220-10226
[2]   PREPARATION AND APPLICATION OF THE 5-(4-(9-FLUORENYLMETHYLOXYCARBONYL)AMINOMETHYL-3,5-DIMETHOXYPHENOXY)VALERIC ACID (PAL) HANDLE FOR THE SOLID-PHASE SYNTHESIS OF C-TERMINAL PEPTIDE AMIDES UNDER MILD CONDITIONS [J].
ALBERICIO, F ;
KNEIBCORDONIER, N ;
BIANCALANA, S ;
GERA, L ;
MASADA, RI ;
HUDSON, D ;
BARANY, G .
JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (12) :3730-3743
[3]  
ALBERICIO F, 1987, INT J PEPT PROT RES, V30, P206
[4]  
Alsina J, 1999, CHEM-EUR J, V5, P2787, DOI 10.1002/(SICI)1521-3765(19991001)5:10<2787::AID-CHEM2787>3.0.CO
[5]  
2-2
[6]   Strong dimerization of ureidopyrimidones via quadruple hydrogen bonding [J].
Beijer, FH ;
Sijbesma, RP ;
Kooijman, H ;
Spek, AL ;
Meijer, EW .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (27) :6761-6769
[7]  
Beijer FH, 1998, ANGEW CHEM INT EDIT, V37, P75, DOI 10.1002/(SICI)1521-3773(19980202)37:1/2<75::AID-ANIE75>3.0.CO
[8]  
2-R
[9]   Design and asymmetric synthesis of beta-strand peptidomimetics [J].
Boumendjel, A ;
Roberts, JC ;
Hu, E ;
Pallai, PV ;
Rebek, J .
JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (13) :4434-4438
[10]   DESICCANT EFFICIENCY IN SOLVENT DRYING .3. DIPOLAR APROTIC-SOLVENTS [J].
BURFIELD, DR ;
SMITHERS, RH .
JOURNAL OF ORGANIC CHEMISTRY, 1978, 43 (20) :3966-3968