Submandibular gland tripeptide FEG (Phe-Glu-Gly) and analogues: keys to structure determination.
This study examined the structure activity relationship of NH(3)-Phe-Glu-Gly-COO(-) (FEG), a potent inhibitor of intestinal anaphylaxis. The inhibition by FEG analogues of antigen-provoked contractions of isolated ileal segments obtained from ovalbumin-sensitized rats was determined and molecular modeling performed. A combination of aromaticity of the first residue, minimal extension of the carboxyl group on residue 2, and underivatized N and C termini were essential for biological activity. FEG, WEG, WDG and the d-enantiomeric forms of FEG (feG) and YEG (yeG) retained biological activity. By considering dipole moments, the structural and conformational features critical to biological activity were established as the glutamyl-carboxyl group/Phe side chain and carboxyl/amino termini interactions. Analysis of Ramachandran plots for position 1 sidechains indicate that mobility of the aromatic sidechain must be restricted to retain biological activity. The anti-anaphylactic effects of FEG, characterized by specific structural and conformational restrictions, indicate a selective interaction with a receptor for this peptide in the intestine.
Metwally
Essam
E
Department of Physiology and Biophysics, The University of Calgary, T2N 4N1, Calgary, Alberta, Canada. emetwall@acs.ucalgary.ca
Pires
Jose M
JM
Moore
Graham J
GJ
Befus
Dean A
DA
Davison
Joseph S
JS
Mathison
Ronald
R
D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology; D010452:Peptide Biosynthesis; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000378:metabolism*
D009842:Oligopeptides; C114891:tripeptide FEG; D001224:Aspartic Acid; D010047:Ovalbumin