Abstract
Coupling of amino acids to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (HOTic) is difficult.In model experiments, use of 1-hydroxy-7-azabenzotriazole(HOAt) in combination with either N,N-diisopropylcarbodiimide (DIC) or O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium (HATU) for activation waseffective in solving coupling difficulties. Based on thisfinding, HOTic was then incorporated into the 20–31 fragmentof human epidermal growth factor (hEGF).[Abu20,31,HOTic22]hEGF(20–31)-NH2was shown to be a 'difficult sequence', but replacement of the Tyr at position 29 with HOTic facilitates the complete dodecapeptide synthesis.
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Bozsó, Z., Tóth, G., Murphy, R.F. et al. Difficulties in coupling to conformationally constrained aromatic amino acids. Letters in Peptide Science 7, 157–163 (2000). https://doi.org/10.1023/A:1008928404072
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DOI: https://doi.org/10.1023/A:1008928404072