A highly active chemotactic peptide analog incorporating the unusual residue 1-aminocyclohexanecarboxylic acid at position 2.
Analogs of chemotactic peptides (Formyl-Met-X-Phe-OMe) containing the stereochemically constrained residues alpha-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Acc5) and 1-aminocyclohexanecarboxylic acid (Acc6) at position 2 are compared with the parent sequence (X = Leu) for their ability to induce lysozyme release in rabbit neutrophils. The Acc6 analog is about 78 times more active than the parent peptide, For-Met-Leu-Phe-OH, whereas Aib and Acc5 analogs are approximately 3 and 2 times, respectively, less active than the parent peptide. NMR and model building studies clearly favour a Met-Acc6 beta-turn solution conformation in the Acc6 analog, suggesting that the neutrophil receptor is capable of recognizing a folded peptide structure. The significant differences in the activities of the Acc5 and Acc6 analogs suggest an important role for the residue 2 sidechain in receptor interactions.
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000818:Animals; D003509:Cyclohexanecarboxylic Acids; D009682:Magnetic Resonance Spectroscopy; D009113:Muramidase / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011817:Rabbits; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; C014966:1-aminocyclohexanecarboxylic acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase