The effect of the cyclopropyl group on the conformation of chemotactic formyl tripeptides.
Certain formyl peptides are powerful chemoattractants towards neutrophils. In this study, several formyl tripeptides were synthesized and used to investigate the effects of different amino acid residues in position 1 on their ability to stimulate neutrophil chemotaxis. Pig neutrophil chemotaxis towards the formyl tripeptide, HCO-Ac(3)C-Leu-Phe-OMe 1, where Ac(3)C represents 1-amino-1-cyclopropane carboxylic acid, was observed. Pig neutrophil chemotaxis towards a very similar formyl tripeptide, HCO-Aib-Leu-Phe-OMe 2, where Aib represents alpha-amino isobutyric acid, was not observed. Compared to the isopropyl group, it was shown that the cyclopropyl group induces a greater percentage of the E conformation about the formamide functionality in these peptides. For 1 and 2, the E isomer distributions in CDCl3 are 36 and 9%, respectively. Since a major difference between these two peptides is the Z/E isomeric distribution, one implication is that the peptide-receptor site interactions involving the E conformer are more effective than those of the Z conformer. No pig neutrophil chemotaxis towards the formyl tripeptides, HCO-Ala-Leu-Phe-OMe 3 and HCO-Gly-Leu-Phe-OMe 4 was observed. These formyl tripeptides exhibit a low percentage of the E isomer, similar to that of peptide 2.
Headley
Allan D
AD
Department of Chemistry and Biochemistry, Texas Tech University, Box 41061, (Memorial Circle & Boston), Lubbock, TX 79409-1061, USA. allan.headley@ttu.edu
Ganesan
Rajeswari
R
Nam
Jaewook
J
D000818:Animals; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003521:Cyclopropanes / Q000737:chemistry*; D005559:Formamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005561:Formates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013552:Swine
D002630:Chemotactic Factors; D003521:Cyclopropanes; D005559:Formamides; D005561:Formates; D009842:Oligopeptides