Design of soymetide-4 derivatives to potentiate the anti-alopecia effect.

Abstract

Previously, we found that soymetide-4 (MITL), an N-formyl-methionyl-leucyl-phenylalanine (fMLP) agonist peptide derived from soybean beta-conglycinin alpha' subunit, stimulated phagocytosis of human polymorphonuclear leukocytes, and inhibited alopecia induced by etoposide, an anticancer drug, in neonatal rats after oral administration. We found that the fMLP receptor affinity and phagocytosis-stimulating activity of soymetide-4 was potentiated by replacement of Thr(3) with hydrophobic residues. Among the derivatives synthesized, [Trp](3)-soymetide-4 (MIWL) was the most potent, stronger by 180 and 130 times than soymetide-4 in receptor affinity and phagocytosis-stimulating activity, respectively. The anti-alopecia effect of [Trp](3)-soymetide-4 was about 3 times larger than that of soymetide-4 after oral administration.

• Authors: Takahiro Tsuruki, Masaaki Yoshikawa
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 68 Issue 5 Pg. 1139-41 (May 2004) ISSN: 0916-8451 [Print] England
• PMID: 15170122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Plant
• Globulins
• Oligopeptides
• Peptide Fragments
• Receptors, Formyl Peptide
• Seed Storage Proteins
• Soybean Proteins
• beta-conglycinin protein, Glycine max
• soymetide-4
• soymetide-4, Thr(3)-
• N-Formylmethionine Leucyl-Phenylalanine

Topics

• Alopecia (chemically induced, drug therapy)
• Amino Acid Substitution
• Animals
• Antigens, Plant
• Disease Models, Animal
• Drug Design
• Globulins (chemistry)
• Humans
• N-Formylmethionine Leucyl-Phenylalanine (agonists)
• Neutrophils (drug effects)
• Oligopeptides (chemistry, pharmacology, therapeutic use)
• Peptide Fragments (chemistry, pharmacology)
• Phagocytosis (drug effects)
• Rats
• Receptors, Formyl Peptide (agonists)
• Seed Storage Proteins
• Soybean Proteins (chemistry, pharmacology)