Summary
In order to obtain antibodies able to catalyse a peptide synthesis, a naive combinatorial library of human Fab antibody fragments was screened with the phosphonamidate transition state analogue of the reaction. Several Fab fragments were able to bind the analogue. Competitive binding studies performed with molecules containing representative parts of the hapten showed that two Fabs were able to recognize specifically the tetrahedral phosphorus present in the hapten.
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Dawson PE, Muir TW, Clark-Lewis I, Kent SBH (1994) Synthesis of proteins by native chemical ligation. Science 266: 776–779
Gaertner HF, Rose K, Cotton R, Timms D, Camble R, Offord RE (1992) Construction of proteins analogues by site-specific condensation of unprotected fragments. Bioconjugate Chem 3: 262–268
Griffiths AD, William SC, Hartley O, Tomlinson IM, Waterhouse P, Croby WL, Kotermann RE, Jones PT, Low NM, Allison TJ, et al (1994) Isolation of high affinity human antibodies directly from large synthetic repertoire. EMBO J 13: 3245–3260
Hariharan M, Chaberek S, Martell AE (1973) Synthesis of phosphonopeptide derivatives. Syn Commun 3: 375–379
Hirschmann R, Smith AB, Taylor CM, Benkovic PA, Taylor SD, Yager KM, Sprengeler PA, Benkovic SJ (1994) Peptide synthesis catalyzed by an antibody containing a binding site for variable amino acids. Science 265: 234–237
Jacobsen JR, Schultz PG (1994) Antibody catalysis of peptide bond formation. Proc Natl Acad Sci 91: 5888–5892
Jakubke H-D (1995) Peptide ligases-tools for peptide synthesis. Angew Chem Int Ed Engl 34: 175–177
Liu C-F, Tam JP (1994) Chemical ligation approach to form a peptide bond between unprotected peptide segments. Concept and model study. J Am Chem Soc 116: 4149–4153
Pollack SJ, Jacobs WJ, Schultz PG (1986) Selective chemical catalysis by an antibody. Science 234: 1570–1573
Stewart JD, Benkovic SJ (1995) Transition-state stabilization as a measure of the efficiency of antibody catalysis. Nature 375: 388–391
Tramontano A, Janda KD, Lerner RA (1986) Catalytic antibodies. Science 234: 1566–1570
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Hua, T.D., Lamaty, F., Souriau, C. et al. Specific recognition of a tetrahedral phosphonamidate transition state analogue group by a recombinant antibody Fab fragment. Amino Acids 10, 167–172 (1996). https://doi.org/10.1007/BF00806589
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DOI: https://doi.org/10.1007/BF00806589