SYNTHESIS AND PROPERTIES OF SOME PEPTIDE ANALOGS OF ACTINOMYCIN-D

被引：20

作者：

MAUGER, AB ^{[1
]}

STUART, OA ^{[1
]}

KATZ, E ^{[1
]}

机构：

[1] GEORGETOWN UNIV, SCH MED, DEPT MICROBIOL, WASHINGTON, DC 20007 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 04期

关键词：

D O I：

10.1021/jm00108a009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Analogues of actinomycin D (AMD) were synthesized in which amino acid replacements were made at various sites in the peptide moieties. These include (i) replacement of both N-methylvalines by N-methylleucine, (ii) replacement of both sarcosines by N-[2-(methoxycarbonyl)ethyl]glycine, and (iii) replacement of one or both D-valines by D-threonine. The purpose of replacements ii and iii was to ascertain the effect upon biological activity of introducing a new side chain which could be functionalized to allow the attachment of carrier molecules such as antibodies. NMR data indicated that none of the analogues had solution conformations significantly different from that of AMD. Difference spectra with DNA revealed that replacement i enhanced binding while the other analogues bound less strongly to DNA. All the analogues had lower antimicrobial activities than AMD. In contrast, 5,5'-(MeLeu)2AMD displayed in vitro antitumor activity comparable with that of AMD at approximately 100-fold lower concentrations.

引用

页码：1297 / 1301

页数：5

共 24 条

[11]

MACFARLANE RD, 1983, ANAL CHEM, V55, P1247, DOI 10.1021/ac00262a002

[12] STUDIES ON BIOLOGICAL-ACTIVITIES OF ACTINOMYCINS Z1 AND Z5 [J].

MASON, K ;

KATZ, E ;

MAUGER, AB .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1974, 160 (02) :402-411

[13] SYNTHESIS OF AN ACTINOMYCIN-RELATED PEPTIDE, CYCLO-(THR-D-VAL-PRO-SAR-MEALA), AND CONFORMATIONAL STUDIES BY NUCLEAR MAGNETIC-RESONANCE AND X-RAY CRYSTALLOGRAPHY [J].

MAUGER, AB ;

STUART, OA ;

HIGHET, RJ ;

SILVERTON, JV .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1982, 104 (01) :174-180

[14] NMR-STUDIES OF ACTINOMYCINS VARYING AT THE PROLINE SITES [J].

MAUGER, AB ;

THOMAS, WA .

ORGANIC MAGNETIC RESONANCE, 1981, 17 (03) :186-190

[15] SOLUTION CONFORMATION OF THE ACTINOMYCIN-D RELATED PENTAPEPTIDE LACTONE USING NMR AND MOLECULAR MODELING [J].

MAUGER, AB ;

GALLAGHER, KS ;

SILVERTON, JV ;

FERRETTI, JA .

BIOPOLYMERS, 1989, 28 (10) :1771-1780

[16] CONFORMATION AND DIMERIZATION OF ACTINOMYCIN-RELATED PEPTIDE LACTONES IN SOLUTION AND IN THE SOLID-STATE [J].

MAUGER, AB ;

STUART, OA ;

FERRETTI, JA ;

SILVERTON, JV .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (24) :7154-7163

[17] SYNTHESIS OF ACTINOMYCIN ANALOGUES .I. 3-BENZYLOXY-4-METHYL-2-NITROBENZOYL-6-THREONINE AND RELATED COMPOUNDS [J].

MAUGER, AB ;

WADE, R .

JOURNAL OF THE CHEMICAL SOCIETY, 1965, (MAY) :3126-&

[18]

Mauger AB, 1990, CHEM ANTITUMOR AGENT, P403

[19]

MAUGER AB, 1983, PEPTIDES STRUCTURE F, P789

[20]

Mauger AB, 1980, TOP ANTIBIOT CHEM, P224

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