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Applied Biochemistry and Biotechnology

, Volume 83, Issue 1–3, pp 221–232 | Cite as

Nucleophilic proteolytic antibodies

  • Gennady Gololobov
  • Alfonso Tramontano
  • Sudhir Paul
Article

Abstract

Proteolytic antibodies appear to utilizecatalytic 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 ofactive-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.

Index Entries

Catalytic antibodies phage display serine proteases 

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Copyright information

© Humana Press Inc. 2000

Authors and Affiliations

  • Gennady Gololobov
    • 1
  • Alfonso Tramontano
    • 1
  • Sudhir Paul
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Texas Houston Medical SchoolHouston

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