ENHANCED INVITRO TUMOR-CELL RETENTION AND INTERNALIZATION OF ANTIBODY DERIVATIZED WITH SYNTHETIC PEPTIDES

被引：16

作者：

ANDERSON, DC ^{[1
]}

MANGER, R ^{[1
]}

SCHROEDER, J ^{[1
]}

WOODLE, D ^{[1
]}

BARRY, M ^{[1
]}

MORGAN, AC ^{[1
]}

FRITZBERG, AR ^{[1
]}

机构：

[1] NEOREX CORP, SEATTLE, WA 98119 USA

来源：

BIOCONJUGATE CHEMISTRY | 1993年 / 4卷 / 01期

关键词：

D O I：

10.1021/bc00019a002

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The Fab fragments of two antitumor monoclonal antibodies, NR-ML-05 and NR-LU-10, have been covalently derivatized with synthetic peptides designed to provide secondary sites of attachment to enhance their retention on tumor cells. Analogs of the peptide ''GALA'', an amphipathic peptide previously reported to interact with uncharged lipid bilayers, gave antibody conjugates of different molecular weight and bound peptide stoichiometry when attached to Fab fragments using the heterobifunctional cross-linker sulfo-SMCC. This attached peptide enhanced the retention and internalization of Fab fragments of NR-ML-05 on FEMX human melanoma cells, but not of NR-LU-10 on HT-29 human colon carcinoma cells, indicating that this effect might be specific for individual tumor antigen-antibody systems. This peptide appeared to increase nonspecific interactions of the conjugate with antigen-negative cells. Other membrane-active peptides were also tested. None were as effective as the ''GALA'' analogs. A synthetic ion channel peptide attached to NR-ML-05 Fab exhibited the greatest enhanced internalization of these tested peptides.

引用

页码：10 / 18

页数：9

共 36 条

[21]

PARENTE RA, 1988, J BIOL CHEM, V263, P4724

[22]

PARHAM P, 1986, HDB EXPT IMMUNOLOGY, V1, pCH14

[23]

PARKINS J, COMMUNICATION

[24]

PRESS OW, 1988, CANCER RES, V48, P2249

[25] RADIOLABELED ANTIBODIES [J].

PRESSMAN, D .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1957, 69 (04) :644-650

[26]

RASO V, 1984, J BIOL CHEM, V259, P1143

[27] MEASUREMENT OF PROTEIN USING BICINCHONINIC ACID [J].

SMITH, PK ;

KROHN, RI ;

HERMANSON, GT ;

MALLIA, AK ;

GARTNER, FH ;

PROVENZANO, MD ;

FUJIMOTO, EK ;

GOEKE, NM ;

OLSON, BJ ;

KLENK, DC .

ANALYTICAL BIOCHEMISTRY, 1985, 150 (01) :76-85

[28] PH-DEPENDENT BILAYER DESTABILIZATION BY AN AMPHIPATHIC PEPTIDE [J].

SUBBARAO, NK ;

PARENTE, RA ;

SZOKA, FC ;

NADASDI, L ;

PONGRACZ, K .

BIOCHEMISTRY, 1987, 26 (11) :2964-2972

[29]

TANFORD C, 1961, PHYSICAL CHEM MACROM, P336

[30]

VARKI NM, 1984, CANCER RES, V44, P681

← 1 2 3 4 →