383187-88-0Relevant articles and documents
Kinetically Controlled Stepwise Self-Assembly of AuI-Metallopeptides in Water
Kemper, Benedict,Zengerling, Lydia,Spitzer, Daniel,Otter, Ronja,Bauer, Tobias,Besenius, Pol
, p. 534 - 537 (2018)
The combination of attractive supramolecular interactions of a hydrophobic AuI-metallopeptide with the shielding effect of flexible oligoethylene glycol chains provides access to a stepwise self-assembly of a AuI-metalloamphiphile in water. Kinetic control of the supramolecular polymer morphology is achieved using a temperature-dependent assembly protocol, which yields low dispersity supramolecular polymers (metastable state I) or helical bundled nanorods (state II).
Synthesis and optimization of hyaluronic acid-methotrexate conjugates to maximize benefit in the treatment of osteoarthritis
Homma, Akie,Sato, Haruhiko,Tamura, Tatsuya,Okamachi, Akira,Emura, Takashi,Ishizawa, Takenori,Kato, Tatsuya,Matsuura, Tetsu,Sato, Shigeo,Higuchi, Yoshinobu,Watanabe, Tomoyuki,Kitamura, Hidetomo,Asanuma, Kentaro,Yamazaki, Tadao,Ikemi, Masahisa,Kitagawa, Hironoshin,Morikawa, Tadashi,Ikeya, Hitoshi,Maeda, Kazuaki,Takahashi, Koichi,Nohmi, Kenji,Izutani, Noriyuki,Kanda, Makoto,Suzuki, Ryohchi
experimental part, p. 1062 - 1075 (2010/04/24)
We previously reported that a conjugate of hyaluronic acid (HA) and methotrexate (MTX) could be a prototype for future osteoarthritis drugs having the efficacy of the two clinically validated agents but with a reduced risk of the systemic side effects of MTX by using HA as the drug delivery carrier. To identify a clinical candidate, we attempted optimization of a lead, conjugate 1. Initially, in fragmentation experiments with cathepsins, we optimized the peptide part of HA-MTX conjugates to be simpler and more susceptible to enzymatic cleavage. Then we optimized the peptide, the linker, the molecular weight, and the binding ratio of the MTX of the conjugates to inhibit proliferation of human fibroblast-like synoviocytes in vitro and knee swelling in rat antigen-induced monoarthritis in vivo. Consequently, we found conjugate 30 (DK226) to be a candidate drug for the treatment of osteoarthritis.
Rational design, discovery, and synthesis of a novel series of potent growth hormone secretagogues
Huang,Loew,Funamizu,Mimura,Ishiyama,Hayashida,Okuno,Shimada,Okuyama,Ikegami,Nakano,Inoguchi
, p. 4082 - 4091 (2007/10/03)
In the joint experimental and computational efforts reported here to obtain novel chemical entities as growth hormone secretagogues (GHSs), a small database of peptides and non-peptides known to have GHS activity was used to generate and assess a 3D pharmacophore for this activity. This pharmacophore was obtained using a systematic and efficient procedure, "DistComp", developed in our laboratory. The 3D pharmacophore identified was then used to search 3D databases to explore chemical structures that could be novel GHSs. A number of these were chosen for synthesis and assessment of their ability to release growth hormone (GH) from rat pituitary cells. Among the compounds tested, those with a benzothiazepin scaffold were discovered with micromolar activity. To facilitate lead optimization, a second program, a site-dependent fragment QSAR procedure was developed. This program calculates a library of chemical and physical properties of "fragments" or chemical components in a known pharmacophore and determines which, if any, of these properties are important for the observed activity. The combined use of the 3D pharmacophore and the results of the site-dependent fragment QSAR analysis led to the discovery and synthesis of a novel series of potent GHSs, a number of which had nanomolar in vitro activity.
