Nucleophilic proteolytic antibodies

Gennady Gololobov, Alfonso Tramontano, Sudhir Paul

Research output: Contribution to journalArticle

21 Scopus citations

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

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Keywords

  • Catalytic antibodies
  • Phage display
  • Serine proteases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biotechnology
  • Bioengineering

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