Ergot alkaloids themselves can act as chiral selectors. The publication [104]
compares the stereoselectivities of several ergot alkaloids added to the background electrolyte towards some racemic hydroxy organic acids. The 1-allyl
derivative of (5R,8S,10R)-terguride (allyl-TER) proved to be the best chiral
selector. The differential pulse voltametric behavior of ergot alkaloids was
studied [105] in respect of the effects of pH and composition of media and an
automated FIA system with amperometric detection has been used to develop
a selective and sensitive method for the routine quantitative assay of the
alkaloids. In another study, the oxidative electrode reaction of lysergic acidtype ergot alkaloids was described [106] which provides a theoretical and experimental basis for liquid chromatographic or flow-injection determination
with amperometric detection of the alkaloids.
Shelby’s research group has worked on the development of assay systems to
determine ergot alkaloid poisoning by immunological methods. As an example,
ergovaline in tall fescue was detected by a specific monoclonal antibody which
was produced by conjugation of ergovaline and bovine serum albumin. This
antibody was specific for ergot peptide alkaloids with an isopropyl group at the
C(5¢) position of the peptide moiety [107].
A recent development has been the use of two-dimensional fluorescence
spectroscopy as a new method for on-line monitoring of bioprocesses [108]. As
ergot alkaloids fluoresce, the formation of the product during cultivation can be
observed by two-dimensional fluorescence spectroscopy. Substraction spectra
offered on-line real time information about the productivity during the cultivation. It was possible to follow the biomass concentration on-line by monitoring
the culture fluorescence intensity in the region of riboflavine and its derivatives.
This is a powerful application of this new sensor since the on-line determination of biomass is extremely complicated for this fungus.
6
Conclusions
Rapid developments in biotechnology in the last 20 years necessitates the reengineering of our strategies for the achievement of better ergot alkaloids, both
qualitatively and quantitatively. Combinatorial chemistry can tell us which
derivative, be it of tryptophan or lysergic acid, incorporated in the final
molecule would interact with the receptors to give better clinical effects with
lesser side reactions. Today we have advanced software programs which can
combinatorially create thousands of distinct molecules, one atom or functional
group at a time, with real-time assessment of the steric and chemical complementarity of the nascent molecule to the three-dimensional structure of the
receptor site. Notwithstanding the complexity of fungal genetics, the knowledge
of the amino acid and nucleotide sequences of the alkaloid biosynthesis specific
enzymes would give us the chance to modify the active sites by altering the
amino acids in such a way that the engineered active site shows better binding
characteristics with new synthons. The application of mathematical models and
metabolic flux analysis would give a rational approach to the large scale production of ergot alkaloids. Although newer techniques such as capillary electroProgress and Prospects of Ergot Alkaloid Research
17
compares the stereoselectivities of several ergot alkaloids added to the background electrolyte towards some racemic hydroxy organic acids. The 1-allyl
derivative of (5R,8S,10R)-terguride (allyl-TER) proved to be the best chiral
selector. The differential pulse voltametric behavior of ergot alkaloids was
studied [105] in respect of the effects of pH and composition of media and an
automated FIA system with amperometric detection has been used to develop
a selective and sensitive method for the routine quantitative assay of the
alkaloids. In another study, the oxidative electrode reaction of lysergic acidtype ergot alkaloids was described [106] which provides a theoretical and experimental basis for liquid chromatographic or flow-injection determination
with amperometric detection of the alkaloids.
Shelby’s research group has worked on the development of assay systems to
determine ergot alkaloid poisoning by immunological methods. As an example,
ergovaline in tall fescue was detected by a specific monoclonal antibody which
was produced by conjugation of ergovaline and bovine serum albumin. This
antibody was specific for ergot peptide alkaloids with an isopropyl group at the
C(5¢) position of the peptide moiety [107].
A recent development has been the use of two-dimensional fluorescence
spectroscopy as a new method for on-line monitoring of bioprocesses [108]. As
ergot alkaloids fluoresce, the formation of the product during cultivation can be
observed by two-dimensional fluorescence spectroscopy. Substraction spectra
offered on-line real time information about the productivity during the cultivation. It was possible to follow the biomass concentration on-line by monitoring
the culture fluorescence intensity in the region of riboflavine and its derivatives.
This is a powerful application of this new sensor since the on-line determination of biomass is extremely complicated for this fungus.
6
Conclusions
Rapid developments in biotechnology in the last 20 years necessitates the reengineering of our strategies for the achievement of better ergot alkaloids, both
qualitatively and quantitatively. Combinatorial chemistry can tell us which
derivative, be it of tryptophan or lysergic acid, incorporated in the final
molecule would interact with the receptors to give better clinical effects with
lesser side reactions. Today we have advanced software programs which can
combinatorially create thousands of distinct molecules, one atom or functional
group at a time, with real-time assessment of the steric and chemical complementarity of the nascent molecule to the three-dimensional structure of the
receptor site. Notwithstanding the complexity of fungal genetics, the knowledge
of the amino acid and nucleotide sequences of the alkaloid biosynthesis specific
enzymes would give us the chance to modify the active sites by altering the
amino acids in such a way that the engineered active site shows better binding
characteristics with new synthons. The application of mathematical models and
metabolic flux analysis would give a rational approach to the large scale production of ergot alkaloids. Although newer techniques such as capillary electroProgress and Prospects of Ergot Alkaloid Research
17