DIRECTED EVOLUTION OF A PROTEIN - SELECTION OF POTENT NEUTROPHIL ELASTASE INHIBITORS DISPLAYED ON M13 FUSION PHAGE

被引：183

作者：

ROBERTS, BL ^{[1
]}

MARKLAND, W ^{[1
]}

LEY, AC ^{[1
]}

KENT, RB ^{[1
]}

WHITE, DW ^{[1
]}

GUTERMAN, SK ^{[1
]}

LADNER, RC ^{[1
]}

机构：

[1] PROT ENGN CORP,CAMBRIDGE,MA 02138

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1992年 / 89卷 / 06期

关键词：

DISPLAY PHAGE; LIBRARY FRACTIONATION; PROTEASE INHIBITOR; KUNITZ DOMAIN;

D O I：

10.1073/pnas.89.6.2429

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inhibitors of human neutrophil elastase were engineered by designing and producing a library of phage-displayed protease inhibitory domains derived from wild-type bovine pancreatic trypsin inhibitor and fractionating the library for binding to the target protease. The affinity of one of the engineered variants for human neutrophil elastase (K(d) = 1.0 pM) is 3.6 x 10(6)-fold higher than that of the parental protein and exceeds the highest affinity reported for any reversible human neutrophil elastase inhibitor by 50-fold. Thus the display phage method has allowed us to obtain protein derivatives that exhibit greatly increased affinity for a predetermined target. The technology can be applied to design high-affinity proteins for a wide variety of target molecules.

引用

页码：2429 / 2433

页数：5

共 29 条

[1]

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[2]

Ausubel FM, 1987, CURRENT PROTOCOLS MO, V1-5

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