Linear basic peptides for targeting interferon-gamma-glycosaminoglycan interactions: synthesis and inhibitory properties.
Glycosaminoglycans (GAGs) play an important role in inflammatory responses due to their ability to interact with cytokines and chemokines, resulting in the localization of these mediators to specific anatomical sites, where they function to direct leukocyte recruitment and activation. Targeting GAG-cytokine/chemokine interactions might may thus have therapeutic applications as anti-inflammatory or immunomodulatory therapy in vivo. Peptides that mimic the heparin-binding domains of cytokines may have a potential use as inhibitors of GAG-cytokine interactions. A linear octapeptide (MC-2) derived from the conserved heparin-binding region of interferon-gamma (IFN-gamma) was synthesized along with four analogs featuring a substitution of Phe for Leu in position 1 and varying number of positive charges on the octapeptide molecule. The relative abilities of the synthesized peptides to inhibit the interactions between IFN-gamma and GAGs were compared. From the results, it follows that the inhibitory potency of the octapeptide analogs was related to the number of positive charges in the molecule, while increased hydrophobicity had no significant effect.
Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY 40292, USA. rafael@louisville.edu
R
R
Fernandez-Botran
P
P
Romanovskis
X
X
Sun
A F
AF
Spatola
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001667:Binding, Competitive; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006025:Glycosaminoglycans; D009842:Oligopeptides; D010455:Peptides; D007371:Interferon-gamma; D006493:Heparin