Solid-phase synthesis of chemotactic peptides using alpha-azido acids.
Four chemotactic peptides, For-Met-Xxx-Phe-OMe, with an alpha,alpha-disubstituted amino acid at position 2 have been synthesized by the azido acid method [Meldal M, Juliano MA, Jansson AM. 1997. Azido acids in a novel method of solid-phase peptide synthesis. Tetrahedron Lett. 38: 2531-2534] on solid-phase, and were tested for biological activity. Dipropylglycine in the central position (Xxx) was found to be as active as the natural chemotactic peptide for chemotactic activity toward human neutrophils. Higher yields were obtained than previously reported solution-phase syntheses of chemotactic peptides, and EEDQ was used successfully for the difficult solid-phase formylation of amino groups.
Tornøe
C W
CW
Department of Chemistry, Carlsberg Laboratory, Copenhagen, Denmark.
Sengeløv
H
H
Meldal
M
M
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D018000:Receptors, Peptide / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D001386:Azides; D002630:Chemotactic Factors; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium