title: Synthesis and characterization of monodisperse poly(ethylene glycol)-conjugated collagen pentapeptides with collagen biosynthesis-stimulating activity.
abstract: Although collagen pentapeptide (Lys-Thr-Thr-Lys-Ser, KTTKS) has received a great deal of attention owing to its collagen biosynthesis-stimulating effects, its enzymatic instability in the skin is an obstacle to effective topical application. PEGylation is a useful approach for improving the chemical and biological stability of peptides. However, the polydispersity of poly(ethylene glycol) (PEG) produces conjugates with different molecular sizes, which may create difficulties in chemical characterization and purity control, and in variability of biological properties. To overcome these difficulties, monodisperse PEG was site-specifically conjugated to the N-terminal amine of KTTKS to produce a single molecular conjugate, enabling more complete chemical characterization and more exact product specifications. PEG-KTTKS conjugates prepared using monodisperse PEG with two different molecular weights, monodisperse PEG220 and PEG572, were characterized by mass spectrometry. These monodisperse PEG-KTTKS conjugates showed no cytotoxicity (1-100 μM) and stimulated collagen biosynthesis in human skin fibroblasts. They also had high stability against proteolytic enzymes in rat skin. This study demonstrates the usefulness of monodisperse PEG for preparing chemically defined conjugates and suggests that monodisperse PEG-KTTKS would be a good candidate for use as a collagen biosynthesis-stimulating agent.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Myung Sun
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: dhna@knu.ac.kr.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Na
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
chemical_list: D009842:Oligopeptides; D011092:Polyethylene Glycols; C525923:lysyl-threonyl-threonyl-lysyl-serine; D003094:Collagen
keywords: Collagen pentapeptide; Monodisperse poly(ethylene glycol); PEGylation; Stability