title: PEG conjugates of potent α4 integrin inhibitors, maintaining sustained levels and bioactivity in vivo, following subcutaneous administration.
abstract: Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats.
authors.affiliation: Elan Pharmaceuticals, 180 Oyster Point Blvd., South San Francisco, CA 94080, USA.
authors.forename: Jenifer L
authors.initials: JL
authors.lastname: Smith
authors.forename: Kassandra I
authors.initials: KI
authors.lastname: Rossiter
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Semko
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Xu
authors.forename: David A
authors.initials: DA
authors.lastname: Quincy
authors.forename: Jacek
authors.initials: J
authors.lastname: Jagodzinski
authors.forename: Michael S
authors.initials: MS
authors.lastname: Dappen
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Christopher
authors.initials: C
authors.lastname: Vandevert
authors.forename: Caroline
authors.initials: C
authors.lastname: Garrido
authors.forename: Wenxian
authors.initials: W
authors.lastname: Mao
authors.forename: F Bong
authors.initials: FB
authors.lastname: San Pablo
authors.forename: Brian
authors.initials: B
authors.lastname: Wipke
authors.forename: Lilibeth
authors.initials: L
authors.lastname: Dofiles
authors.forename: Angie
authors.initials: A
authors.lastname: Wadsworth
authors.forename: Eric
authors.initials: E
authors.lastname: Peterson
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzana
authors.forename: Stellanie
authors.initials: S
authors.lastname: Simmonds
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Messersmith
authors.forename: Frederique
authors.initials: F
authors.lastname: Bard
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pleiss
authors.forename: Ted A
authors.initials: TA
authors.lastname: Yednock
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D004952:Esters; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D039441:Integrin alpha4 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D004952:Esters; D039441:Integrin alpha4; D011092:Polyethylene Glycols