A novel linker for the solid phase synthesis of peptide amides is described. This linker based on 2-alkoxydibenzocycloheptadiene enables release of the peptide derivative under very mild conditions and is compatible with base labile N-alpha protecting groups. The efficacy of this linker in generating c-terminal peptide amides has been demonstrated in the synthesis of the natural products, little gastrin, big gastrin, substance P and bombesin. Modification of the linker allows peptide hydrazides to be prepared. The use of the linker in producing unprotected peptide hydrazides has been exemplified in the synthesis of the ubiquitin fragments (43-47)NHNH2 and(67-76)NHNH2. Use of the linker for the synthesis of fully protected peptide hydrazides requires further development. Initial experiments indicate that the linker, when appropriately substituted, may also be useful for the solid phase synthesis of fully protected peptide free acids to be used in fragment condensation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666259 |
| Date | January 1990 |
| Creators | McInnes, Campbell |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12616 |
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