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Screening a random pentapeptide library, composed of 14 D-amino acids, against the COOH-terminal sequence of fructose-1,6-bisphosphate aldolase from Trypanosoma brucei

(1997) JOURNAL OF BIOLOGICAL CHEMISTRY. 272(17). p.11378-11383
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Abstract
A random pentapeptide library composed of 14 D-amino acids, including two unusual amino acids, thus representing 537,824 different peptide sequences anchored on polystyrene beads was created with each bead bearing a single pentapeptide sequence. This library was used for affinity screening against the fructose-1,6-bisphosphate aldolase of Trypanosoma brucei labeled with biotin as well as versus the COOH-terminal labeled with fluorescein isothiocyanate. The thus selected peptide beads were identified and the appropriate sequences synthesized as peptide amides and evaluated for enzyme activity inhibition. Screening against the whole enzyme did not result in selection of an enzyme inhibitor. However, we demonstrate here that screening against a part of the enzyme involved in the catalytic activity may lead to the discovery of an enzyme inhibitor as well as an enzyme activator. Two low affin ity inhibitors, RRVKF-NH2 and KThiKAR-NH2, with an IC50 of approximate to 1 mM and approximate to 0.2 mM, respectively, were identified. Two other pentapeptides with the sequence SWChaKK-NH2 and SKChaKM-NH2 are able to activate the enzyme fructose 1,6-bisphosphate aldolase. Thus, successful screening of solid phase libraries can be accomplished using selected sequences of the target enzyme.
Keywords
GENES, BINDING, INHIBITOR, EXPRESSION, SYNTHETIC PEPTIDE LIBRARY, FRUCTOSE-BISPHOSPHATE ALDOLASE

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Chicago
Samson, Isabelle, Jef Rozenski, Bart Samyn, Arthur Van Aerschot, Jozef Van Beeumen, and Piet Herdewijn. 1997. “Screening a Random Pentapeptide Library, Composed of 14 D-amino Acids, Against the COOH-terminal Sequence of Fructose-1,6-bisphosphate Aldolase from Trypanosoma Brucei.” Journal of Biological Chemistry 272 (17): 11378–11383.
APA
Samson, Isabelle, Rozenski, J., Samyn, B., Van Aerschot, A., Van Beeumen, J., & Herdewijn, P. (1997). Screening a random pentapeptide library, composed of 14 D-amino acids, against the COOH-terminal sequence of fructose-1,6-bisphosphate aldolase from Trypanosoma brucei. JOURNAL OF BIOLOGICAL CHEMISTRY, 272(17), 11378–11383.
Vancouver
1.
Samson I, Rozenski J, Samyn B, Van Aerschot A, Van Beeumen J, Herdewijn P. Screening a random pentapeptide library, composed of 14 D-amino acids, against the COOH-terminal sequence of fructose-1,6-bisphosphate aldolase from Trypanosoma brucei. JOURNAL OF BIOLOGICAL CHEMISTRY. 1997;272(17):11378–83.
MLA
Samson, Isabelle, Jef Rozenski, Bart Samyn, et al. “Screening a Random Pentapeptide Library, Composed of 14 D-amino Acids, Against the COOH-terminal Sequence of Fructose-1,6-bisphosphate Aldolase from Trypanosoma Brucei.” JOURNAL OF BIOLOGICAL CHEMISTRY 272.17 (1997): 11378–11383. Print.
@article{183067,
  abstract     = {A random pentapeptide library composed of 14 D-amino acids, including two unusual amino acids, thus representing 537,824 different peptide sequences anchored on polystyrene beads was created with each bead bearing a single pentapeptide sequence. This library was used for affinity screening against the fructose-1,6-bisphosphate aldolase of Trypanosoma brucei labeled with biotin as well as versus the COOH-terminal labeled with fluorescein isothiocyanate. The thus selected peptide beads were identified and the appropriate sequences synthesized as peptide amides and evaluated for enzyme activity inhibition. Screening against the whole enzyme did not result in selection of an enzyme inhibitor. However, we demonstrate here that screening against a part of the enzyme involved in the catalytic activity may lead to the discovery of an enzyme inhibitor as well as an enzyme activator. Two low affin ity inhibitors, RRVKF-NH2 and KThiKAR-NH2, with an IC50 of approximate to 1 mM and approximate to 0.2 mM, respectively, were identified. Two other pentapeptides with the sequence SWChaKK-NH2 and SKChaKM-NH2 are able to activate the enzyme fructose 1,6-bisphosphate aldolase. Thus, successful screening of solid phase libraries can be accomplished using selected sequences of the target enzyme.},
  author       = {Samson, Isabelle and Rozenski, Jef and Samyn, Bart and Van Aerschot, Arthur and Van Beeumen, Jozef and Herdewijn, Piet},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {GENES,BINDING,INHIBITOR,EXPRESSION,SYNTHETIC PEPTIDE LIBRARY,FRUCTOSE-BISPHOSPHATE ALDOLASE},
  language     = {eng},
  number       = {17},
  pages        = {11378--11383},
  title        = {Screening a random pentapeptide library, composed of 14 D-amino acids, against the COOH-terminal sequence of fructose-1,6-bisphosphate aldolase from Trypanosoma brucei},
  url          = {http://dx.doi.org/10.1074/jbc.272.17.11378},
  volume       = {272},
  year         = {1997},
}

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