Two dialkoxynaphthalene aldehydes as backbone amide linkers for solid-phase synthesis.
Two new solid-phase handles for backbone amide anchoring based on regioisomeric dialkoxynaphthalene aldehydes (NALdehydes) were synthesized in five convenient steps from the corresponding commercially available dihydroxynaphthalenes. The two NALdehydes were coupled to an aminomethyl polystyrene support, the first monomer attached by efficient reductive amination, and the secondary amine acylated to form naphthalene amide linker (NAL-1 and NAL-2) anchoring. After on-resin synthesis, release of peptides was effected with TFA/H(2)O (95:5), TFA/DCM (50:50), or low TFA concentrations. The properties of the NAL handles were evaluated in the solid-phase synthesis of a series of peptides, in which NAL-2 showed the best cleavage properties.
Boas
Ulrik
U
Chemical Laboratory II, University of Copenhagen, Universitetsparken 5, DK-2100, Denmark.
Christensen
Jørn B
JB
Jensen
Knud J
KJ
D000215:Acylation; D000409:Alanine / Q000737:chemistry; D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D000586:Amination; D002851:Chromatography, High Pressure Liquid; D005998:Glycine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry
D000447:Aldehydes; D000577:Amides; D009281:Naphthalenes; D010455:Peptides; C031721:naphthalene; D000409:Alanine; D005998:Glycine