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) |
|---|---|
| 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 |
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Keywords
- Catalytic antibodies
- Phage display
- Serine proteases
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biotechnology
- Bioengineering
Cite this
Nucleophilic proteolytic antibodies. / Gololobov, Gennady; Tramontano, Alfonso; Paul, Sudhir.
In: Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology, Vol. 83, No. 1-3, 2000, p. 221-232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nucleophilic proteolytic antibodies
AU - Gololobov, Gennady
AU - Tramontano, Alfonso
AU - Paul, Sudhir
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Catalytic antibodies
KW - Phage display
KW - Serine proteases
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UR - http://www.scopus.com/inward/citedby.url?scp=0034078218&partnerID=8YFLogxK
M3 - Article
C2 - 10826962
AN - SCOPUS:0034078218
VL - 83
SP - 221
EP - 232
JO - Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology
JF - Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology
SN - 0273-2289
IS - 1-3
ER -