47415-56-5Relevant academic research and scientific papers
Interstrand Aminoacyl Transfer in a tRNA Acceptor Stem-Overhang Mimic
Bjork, Samuel J.,Liu, Ziwei,Su, Meng,Sutherland, John D.,Wu, Long-Fei
supporting information, p. 11836 - 11842 (2021/08/03)
Protein-catalyzed aminoacylation of the 3′-overhang of tRNA by an aminoacyl-adenylate could not have taken place prior to the advent of genetically coded peptide synthesis, and yet the latter process has an absolute requirement for aminoacyl-tRNA. There must therefore have been an earlier nonprotein-catalyzed means of generating aminoacyl-tRNA. Here, we demonstrate efficient interstrand aminoacyl transfer from an aminoacyl phosphate mixed anhydride at the 5′-terminus of a tRNA acceptor stem mimic to the 2′,3′-diol terminus of a short 3′-overhang. With certain five-base 3′-overhangs, the transfer of an alanyl residue is highly stereoselective with the l-enantiomer being favored to the extent of ～10:1 over the d-enantiomer and is much more efficient than the transfer of a glycyl residue. N-Acyl-aminoacyl residues are similarly transferred from a mixed anhydride with the 5′-phosphate to the 2′,3′-diol but with a different dependence of efficiency and stereoselectivity on the 3′-overhang length and sequence. Given a prebiotically plausible and compatible synthesis of aminoacyl phosphate mixed anhydrides, these results suggest that RNA molecules with acceptor stem termini resembling modern tRNAs could have been spontaneously aminoacylated, in a stereoselective and chemoselective manner, at their 2′,3′-diol termini prior to the onset of protein-catalyzed aminoacylation.
Nonpeptide αvβ3 antagonists. Part 10: In vitro and in vivo evaluation of a potent 7-methyl substituted tetrahydro-[1,8]naphthyridine derivative
Breslin, Michael J.,Duggan, Mark E.,Halczenko, Wasyl,Hartman, George D.,Duong, Le T.,Fernandez-Metzler, Carmen,Gentile, Michael A.,Kimmel, Donald B.,Leu, Chih-Tai,Merkle, Kara,Prueksaritanont, Thomayant,Rodan, Gideon A.,Rodan, Sevgi B.,Hutchinson, John H.
, p. 4515 - 4518 (2007/10/03)
Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This ap
