Conformationally constrained chemotactic peptide analogs of high biological activity.
The stereochemically constrained chemotactic peptide analogs, formylmethionyl-alpha-aminoisobutyryl-phenylalanine (formyl-Met-Aib-Phe-OH) and formylmethionylcycloleucinylphenylalanine (formyl-Met-Cyl-Phe-OH) are highly effective in inducing lysosomal enzyme release from rabbit neutrophils. NMR studies of the Aib2 analog in (CD3)2SO favor a folded conformation in which the Phe NH group is inaccessible to solvent. Intramolecularly hydrogen-bonded conformations involving a Met-Aib-beta-turn or a gamma-turn centered at Aib2 are considered. The results suggest that folded conformations may allow highly active interactions with the neutrophil formylpeptide receptor.
D000818:Animals; D002630:Chemotactic Factors / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011487:Protein Conformation; D011817:Rabbits; D013329:Structure-Activity Relationship
D002630:Chemotactic Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine; C040300:N-formylmethionyl-cycloleucyl-phenylalanine; C040301:formylmethionyl-alpha-aminoisobutyryl-phenylalanine; D009113:Muramidase; D005966:Glucuronidase