DIRECT VISUALIZATION OF ENZYME-INHIBITORS USING A PORTION MIXING INHIBITOR LIBRARY CONTAINING A QUENCHED FLUOROGENIC PEPTIDE SUBSTRATE .1. INHIBITORS FOR SUBTILISIN CARLSBERG

被引：56

作者：

MELDAL, M

SVENDSEN, I

机构：

[1] Carlsberg Laboratory, Department of Chemistry, DK-2500 Valby, Copenhagen

来源：

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1995年 / 12期

关键词：

D O I：

10.1039/p19950001591

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A PEGA-resin was derivatized with a 2:1 mixture of 4-hydroxymethylbenzoic acid and Fmoc-Lys(Boc)-OH and the fluorogenic substrate Ac-Y(NO2)FQPLAVK(ABz)-PEGA was assembled using the active ester approach. Following esterification of.-the 4-hydroxymethylbenzoic acid with Fmoc-Val-OH a library X(1)X(2)X(3)-x(4)-X(5)X(6)V was assembled by the portion mixing method. The library was subjected to extensive hydrolysis by subtilisin Carlsberg and the rate of hydrolysis was highly dependent on the potential inhibitor contained in each bead. The most persistently dark beads were collected and sequenced to yield repeatedly highly lipophilic peptides. Some of these were synthesized and found to be strong inhibitors of subtilisin Carlsberg in solution.

引用

页码：1591 / 1596

页数：6

共 25 条

[1]

Auzanneau F I, 1995, J Pept Sci, V1, P31, DOI 10.1002/psc.310010106

[2] AN EFFICIENT METHOD FOR ANCHORING FMOC-AMINO ACIDS TO HYDROXYL-FUNCTIONALIZED SOLID SUPPORTS [J].

BLANKEMEYERMENGE, B ;

NIMTZ, M ;

FRANK, R .

TETRAHEDRON LETTERS, 1990, 31 (12) :1701-1704

[3]

DORSCH D, 1993, KONTAKTE DARMSTADT, P48

[4]

FORSTER T, 1948, ANN PHYS, V6, P55

[5] GENERAL-METHOD FOR RAPID SYNTHESIS OF MULTICOMPONENT PEPTIDE MIXTURES [J].

FURKA, A ;

SEBESTYEN, F ;

ASGEDOM, M ;

DIBO, G .

INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, 1991, 37 (06) :487-493

[6] EXTENSIVE COMPARISON OF THE SUBSTRATE PREFERENCES OF 2 SUBTILISINS AS DETERMINED WITH PEPTIDE-SUBSTRATES WHICH ARE BASED ON THE PRINCIPLE OF INTRAMOLECULAR QUENCHING [J].

GRON, H ;

MELDAL, M ;

BREDDAM, K .

BIOCHEMISTRY, 1992, 31 (26) :6011-6018

[7] DE-NOVO DESIGN AND SYNTHESIS OF SOMATOSTATIN NONPEPTIDE PEPTIDOMIMETICS UTILIZING BETA-D-GLUCOSE AS A NOVEL SCAFFOLDING [J].

HIRSCHMANN, R ;

NICOLAOU, KC ;

PIETRANICO, S ;

LEAHY, EM ;

SALVINO, J ;

ARISON, B ;

CICHY, MA ;

SPOORS, PG ;

SHAKESPEARE, WC ;

SPRENGELER, PA ;

HAMLEY, P ;

SMITH, AB ;

REISINE, T ;

RAYNOR, K ;

MAECHLER, L ;

DONALDSON, C ;

VALE, W ;

FREIDINGER, RM ;

CASCIERI, MR ;

STRADER, CD .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (26) :12550-12568

[8]

HOLM A, 1989, PEPTIDES 1988, P208

[9] NEW COUPLING REAGENTS IN PEPTIDE CHEMISTRY [J].

KNORR, R ;

TRZECIAK, A ;

BANNWARTH, W ;

GILLESSEN, D .

TETRAHEDRON LETTERS, 1989, 30 (15) :1927-1930

[10] DIRECT DESIGN OF A POTENT NONPEPTIDE FIBRINOGEN RECEPTOR ANTAGONIST BASED ON THE STRUCTURE AND CONFORMATION OF A HIGHLY CONSTRAINED CYCLIC RGD PEPTIDE [J].

KU, TW ;

ALI, FE ;

BARTON, LS ;

BEAN, JW ;

BONDINELL, WE ;

BURGESS, JL ;

CALLAHAN, JF ;

CALVO, RR ;

CHEN, LC ;

EGGLESTON, DS ;

GLEASON, JG ;

HUFFMAN, WF ;

HWANG, SM ;

JAKAS, DR ;

KARASH, CB ;

KEENAN, RM ;

KOPPLE, KD ;

MILLER, WH ;

NEWLANDER, KA ;

NICHOLS, A ;

PARKER, MF ;

PEISHOFF, CE ;

SAMANEN, JM ;

UZINSKAS, I ;

VENSLAVSKY, JW .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (19) :8861-8862

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