ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS

GROEGER C, Wenzel H, Tschesche H (1991)
JOURNAL OF PROTEIN CHEMISTRY 10(2): 245-251.

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Abstract
The replacement of amino acids in the P1' and P2' position of aprotinin, the bovine pancreatic trypsin inhibitor, is described. Using the "modified" inhibitor as starting material, with the hydrolyzed reactive-site peptide bond Lys15-Ala16, the residues P1' (Ala16) and P2' (Arg17) were split off by the action of aminopeptidase K. Incorporation of suitable dipeptides containing a basic residue (Lys or Arg) in the C-terminal position was carried out in a "one pot" reaction involving trypsin-catalyzed coupling. In this way, the native fragment Ala16-Arg17 was reintroduced and also replaced by Gly-Arg, Ala-Lys, and Leu-Arg yielding intact inhibitor molecules. The mechanism for incorporation of dipeptides was investigated by treating the aprotinin derivative with the Arg17-Ile18 peptide bond hydrolyzed with trypsin under proteosynthetic conditions. We established that only inhibitor molecules cleaved between Lys15 and Xaa16 are intermediates leading to the desired products. The inhibitory properties of the new aprotinin homologues were tested, and the significance of the P1' residue for the inhibition of trypsin, kallikrein, and chymotrypsin was deduced.
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GROEGER C, Wenzel H, Tschesche H. ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS. JOURNAL OF PROTEIN CHEMISTRY. 1991;10(2):245-251.
GROEGER, C., Wenzel, H., & Tschesche, H. (1991). ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS. JOURNAL OF PROTEIN CHEMISTRY, 10(2), 245-251.
GROEGER, C., Wenzel, H., and Tschesche, H. (1991). ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS. JOURNAL OF PROTEIN CHEMISTRY 10, 245-251.
GROEGER, C., Wenzel, H., & Tschesche, H., 1991. ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS. JOURNAL OF PROTEIN CHEMISTRY, 10(2), p 245-251.
C. GROEGER, H. Wenzel, and H. Tschesche, “ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS”, JOURNAL OF PROTEIN CHEMISTRY, vol. 10, 1991, pp. 245-251.
GROEGER, C., Wenzel, H., Tschesche, H.: ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS. JOURNAL OF PROTEIN CHEMISTRY. 10, 245-251 (1991).
GROEGER, C, Wenzel, Herbert, and Tschesche, Harald. “ENZYMATIC SEMISYNTHESIS OF APROTININ HOMOLOGS MUTATED IN P' POSITIONS”. JOURNAL OF PROTEIN CHEMISTRY 10.2 (1991): 245-251.
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5 Citations in Europe PMC

Data provided by Europe PubMed Central.

Immobilized protease-assisted synthesis of engineered cysteine-knot microproteins.
Thongyoo P, Jaulent AM, Tate EW, Leatherbarrow RJ., Chembiochem 8(10), 2007
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Bongers J, Heimer EP., Peptides 15(1), 1994
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Recombinant aprotinin homologue with new inhibitory specificity for cathepsin G.
Brinkmann T, Schnierer S, Tschesche H., Eur. J. Biochem. 202(1), 1991
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