PEGylation of an osteoclast inhibitory peptide: suitable candidate for the treatment of osteoporosis.
Osteoporosis is a condition of bone loss due to excessive osteoclastic activity. Several protein factors, such as receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), have been identified that are important in the pathogenesis of osteoporosis. RANKL binds to RANK and activates the NF-κB pathway by interaction of its cytoplasmic domain with an intracellular adapter protein, TNF receptor associated factors 6 (TRAF 6). This interaction can be inhibited by cell-permeable peptides that prevent RANK-TRAF 6 interaction. However, similar to the peptides/proteins used in clinical setting, the effective application of this TRAF 6 Inhibitory peptide as a therapeutic agent is marred by several limitations for instance short half-life, rapid renal clearance and immunogenicity. In the present study, we have developed PEGylated TRAF 6 Inhibitory peptide by conjugating TRAF 6 Inhibitory peptide to linear PEG backbone that exhibits longer bioavailability in plasma in the animal model. Besides, it has an enhanced uptake at its site of action, i.e., bone marrow.
IMGENEX India Pvt. Ltd., E-5, Infocity, Bhubaneswar, India.
Jabed
J
Akhtar
Vandana
V
Mallaredy
Jagneshwar
J
Dandapat
Prasanta
P
Maiti
Sanjeeb K
SK
Sahoo
Sujay
S
Singh
D000818:Animals; D001682:Biological Availability; D001853:Bone Marrow / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006207:Half-Life; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors*
D010455:Peptides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D048029:TNF Receptor-Associated Factor 6; D011092:Polyethylene Glycols