Head-to-tail cyclized cystine-knot peptides by a combined recombinant and chemical route of synthesis

被引:25
作者
Avrutina, Olga [1 ]
Schmoldt, Hans-Ulrich [1 ,5 ]
Gabrijelcic-Geiger, Dusica [3 ]
Wentzel, Alexander [4 ]
Frauendorf, Holm [2 ]
Sommerhoff, Christian P. [3 ]
Diederichsen, Ulf [2 ]
Kolmar, Harald [1 ]
机构
[1] Tech Univ Darmstadt, Inst Organ Chem & Biochem, D-64287 Darmstadt, Germany
[2] Univ Gottingen, Inst Organ & Biomol Chem, D-37077 Gottingen, Germany
[3] Ludwig Maximillians Univ Klinikum, Klin Chem & Klin Biochem Abt, D-80336 Munich, Germany
[4] Selecore GmbH, D-37079 Gottingen, Germany
[5] Nascacell Technol AG, D-81377 Munich, Germany
关键词
cyclic peptides; cystine knot miniproteins; hydrazones; inhibitors; macrocyclization; protein modifications;
D O I
10.1002/cbic.200700452
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Backbone cyclization of recombinantly produced cystine knot peptides, resulting in correctly folded macrocyclic disulfide-bridged peptides, is reported. It does not require protecting groups, takes place in aqueous solution, and is devoid of racemization and solubility problems. Scaling up to production of multimilligram amounts of iminocyclotides seems feasible. The resulting iminocyclotides are biologically active proteinase inhibitors - imino-cyclo-McoEe-TIKKV was identified as the most potent proteinaceous inhibitor of human mast cell tryptase known. (Figure Presented) © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:33 / 37
页数:5
相关论文
共 61 条
[1]  
[Anonymous], RUSSIAN CHEM REV
[2]   Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II [J].
Avrutina, O ;
Schmoldt, HU ;
Gabrijelcic-Geiger, D ;
Le Nguyen, D ;
Sommerhoff, CP ;
Diederichsen, U ;
Kolmar, H .
BIOLOGICAL CHEMISTRY, 2005, 386 (12) :1301-1306
[3]   FMOC-assisted synthesis of a 29-residue cystine-knot trypsin inhibitor containing a guaninyl amino acid at the P1-position [J].
Avrutina, O ;
Schmoldt, HU ;
Kolmar, H ;
Diederichsen, U .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2004, 2004 (23) :4931-4935
[4]   Rescuing a destabilized protein fold through backbone cyclization [J].
Camarero, JA ;
Fushman, D ;
Sato, S ;
Giriat, I ;
Cowburn, D ;
Raleigh, DP ;
Muir, TW .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 308 (05) :1045-1062
[5]   Biosynthesis of a fully functional cyclotide inside living bacterial cells [J].
Camarero, Julio A. ;
Kimura, Richard H. ;
Woo, Youn-Hi ;
Shekhtman, Alexander ;
Cantor, Jason .
CHEMBIOCHEM, 2007, 8 (12) :1363-1366
[6]   USE OF RESTRAINED MOLECULAR-DYNAMICS IN WATER TO DETERMINE 3-DIMENSIONAL PROTEIN-STRUCTURE - PREDICTION OF THE 3-DIMENSIONAL STRUCTURE OF ECBALLIUM-ELATERIUM TRYPSIN INHIBITOR-II [J].
CHICHE, L ;
GABORIAUD, C ;
HEITZ, A ;
MORNON, JP ;
CASTRO, B ;
KOLLMAN, PA .
PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1989, 6 (04) :405-417
[7]   The cystine knot of a squash-type protease inhibitor as a structural scaffold for Escherichia coli cell surface display of conformationally constrained peptides [J].
Christmann, A ;
Walter, K ;
Wentzel, A ;
Krätzner, R ;
Kolmar, H .
PROTEIN ENGINEERING, 1999, 12 (09) :797-806
[8]   Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif [J].
Craik, DJ ;
Daly, NL ;
Bond, T ;
Waine, C .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (05) :1327-1336
[9]   Plant cyclotides: circular, knotted peptide toxins [J].
Craik, DJ .
TOXICON, 2001, 39 (12) :1809-1813
[10]   Discovery, structure and biological activities of the cyclotides [J].
Craik, DJ ;
Daly, NL ;
Mulvenna, J ;
Plan, MR ;
Trabi, M .
CURRENT PROTEIN & PEPTIDE SCIENCE, 2004, 5 (05) :297-315