Submandibular gland tripeptide FEG (Phe-Glu-Gly) and analogues: keys to structure determination |
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Authors: | Metwally Essam Pires Jose M Moore Graham J Befus Dean A Davison Joseph S Mathison Ronald |
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Institution: | Department of Physiology and Biophysics, The University of Calgary, T2N 4N1, Calgary, Alberta, Canada. emetwall@acs.ucalgary.ca |
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Abstract: | 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. |
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