Abstract
Proteolytic antibodies appear to utilize catalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis and protease- inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target polypeptide could potentially be developed by applying appropriate immunogens and selection strategies. Analysis of transition-state stabilizing interactions suggests that chemical reactivity of active-site serine residues is an important contributor to catalysis. A prototype antigen analog capable of reacting covalently with nucleophilic serine residues permitted enrichment of the catalysts from a phage-displayed lupus light- chain library. Further mechanistic developments in understanding proteolytic antibodies may lead to the isolation of catalysts suitable for passive immunotherapy of major diseases, and elicitation of catalytic immunity as a component of prophylactic vaccination.
Original language | English (US) |
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Pages (from-to) | 221-232 |
Number of pages | 12 |
Journal | Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology |
Volume | 83 |
Issue number | 1-3 |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Catalytic antibodies
- Phage display
- Serine proteases
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biotechnology
- Bioengineering