The development of highly efficient onium-type peptide coupling reagents based upon rational molecular design.
Novel and highly efficient immonium-, pyridinium- and thiazolium-type peptide coupling reagents, such as BOMI, BDMP, BPMP, BEP, FEP, BEPH, FEPH and BEMT, were developed by rational modifying of the molecular structures of commonly used uronium-type reagents. The high efficiency of these onium salts has been evaluated and proven by model reaction tests and the successful synthesis of various oligopeptides and biologically active peptides, both in solution and in the solid-phase, for example Leu-enkephalin, the pentapeptide moiety of Dolastatin 15 and the immunosuppressive undecapeptide cyclosporin O. Based upon these results, the relationship between the molecular structure and the capability of onium-type peptide coupling reagents was studied. A preliminary guideline for the molecular design of onium-type coupling reagents was developed.
Li
P
P
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institute of Health, Frederick, MD 21702, USA. pengli@helix.nih.gov
Xu
J C
JC
D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D007536:Isomerism; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D009861:Onium Compounds / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D009861:Onium Compounds; D010455:Peptides