title: Prooligonucleotides exhibit less serum-protein binding than phosphodiester and phosphorothioate oligonucleotides.
abstract: The protein-binding properties of dodecathymidine derivatives (prooligos) bearing either methyl- or tert-butyl-S-acylthioethyl (Me- or tBuSATE) protecting groups were evaluated. The dissociation constants (Kd) were estimated for complexes of prooligos with serum blood proteins and lactoferrin using prooligos to compete the binding of the radiolabeled, alkylating probe oligonucleotide CIRp(T)12 with the proteins. tBuSATE and MeSATE prooligos have decreased affinity of binding with serum proteins and lactoferrin compared with their parent oligos. These data suggest that prooligos should cause less side effects which combined with their stability to nucleases and enhanced permeability into cells make them potentially useful for design of therapeutics.
authors.affiliation: Laboratoire de Chimie Organique Biomoléculaire de Synthèse, Université de Montpellier II, France.
authors.forename: G
authors.initials: G
authors.lastname: Tosquellas
authors.forename: A
authors.initials: A
authors.lastname: Bryksin
authors.forename: K
authors.initials: K
authors.lastname: Alvarez
authors.forename: F
authors.initials: F
authors.lastname: Morvan
authors.forename: J J
authors.initials: JJ
authors.lastname: Vasseur
authors.forename: B
authors.initials: B
authors.lastname: Rayner
authors.forename: E
authors.initials: E
authors.lastname: Rykova
authors.forename: P
authors.initials: P
authors.lastname: Laktionov
authors.forename: V
authors.initials: V
authors.lastname: Vlassov
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
mesh_terms: D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D002417:Cattle; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D051379:Mice; D009841:Oligonucleotides / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013873:Thionucleotides / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009841:Oligonucleotides; D012709:Serum Albumin; D013873:Thionucleotides; D007781:Lactoferrin; D013936:Thymidine