- Cyclization of all-L-pentapeptides by means of 1-hydroxy-7-azabenzotriazole-derived uronium and phosphonium reagents
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Due to their restricted conformational flexibility, cyclic peptides are of great interest in connection with structure-activity relationships, especially the elucidation of bioactive conformations. For linear peptides that do not contain turn structure-inducing amino acid residues, the cyclization reaction may be an inherently improbable or slow process, and side reactions, such as cyclodimerization and epimerization at the C-terminal residue, may dominate. A number of 1-hydroxy-7-azabenzotriazole-based onium salts were examined for cyclization of thymopentin-derived pentapeptides and the results compared with data from more conventional coupling reagents. The azabenzotriazol-derived coupling reagents stood out as being the most effective by far. The cyclizations proceed extremely rapidly, and in contrast to other coupling reagents, C-terminal epimerization was generally less than 10%. C-terminal D-amino acid residues favor the formation of monocyclic pentapeptide rings. A similar effect was observed for cyclization of linear N-methylamino acid-containing peptides, suggesting that reversible amide bond alkylation such as Hmb-modification should be useful in promoting the cyclization of pepitdes devoid of turn-inducing amino acid residues.
- Ehrlich, Angelika,Heyne, Hans-Ulrich,Winter, Ruediger,Beyermann, Michael,Haber, Hanka,Carpino, Louis A.,Bienert, Michael
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- SYNTHESIS AND NMR INVESTIGATION OF CYCLIC PENTAPEPTIDE ANALOGUES OF THYMOPENTIN
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The synthesis of two cyclic pentapeptides cyclo(-Arg-Lys-Xxx-D-Val-Tyr-) (Xxx= Asp or Glu) with thymopentin-analogue sequences is described.Cyclization was achieved by the carbodiimide/DMAP method.The results of the NMR investigations performed on the pro
- Kessler, Horst,Kutscher, Bernhard
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p. 177 - 180
(2007/10/02)
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