Nucleophilic proteolytic antibodies

Gennady Gololobov, Alfonso Tramontano, Sudhir Paul

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)221-232
Number of pages12
JournalApplied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology
Volume83
Issue number1-3
StatePublished - 2000
Externally publishedYes

Fingerprint

Antibodies
Serine
Catalysts
Passive Immunization
Serine Proteases
Protease Inhibitors
Catalysis
Mutagenesis
Bacteriophages
Libraries
Immunity
Catalytic Domain
Chemical reactivity
Vaccination
Polypeptides
Antigens
Light
Ground state
Peptides
Peptide Hydrolases

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 journalArticle

Gololobov, G, Tramontano, A & Paul, S 2000, 'Nucleophilic proteolytic antibodies', Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology, vol. 83, no. 1-3, pp. 221-232.
Gololobov, Gennady ; Tramontano, Alfonso ; Paul, Sudhir. / Nucleophilic proteolytic antibodies. In: Applied Biochemistry and Biotechnology - Part A Enzyme Engineering and Biotechnology. 2000 ; Vol. 83, No. 1-3. pp. 221-232.
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