Anna-Maria A. Hays Putnam
Eli Lilly and Company
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Anna-Maria A. Hays Putnam.
Proceedings of the National Academy of Sciences of the United States of America | 2011
Ho Cho; Tom Daniel; Ying Buechler; David C. Litzinger; Zhenwei Maio; Anna-Maria A. Hays Putnam; Bee-Cheng Sim; Stuart Bussell; Tsotne Javahishvili; Sami Kaphle; Guillermo Viramontes; Mike Ong; Stephanie Chu; Becky Gc; Ricky Lieu; Nick Knudsen; Paola Castiglioni; Thea Norman; Douglas W. Axelrod; Andrew R. Hoffman; Peter G. Schultz; Richard D. DiMarchi; Bruce E. Kimmel
The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
Diabetes | 2012
James Mu; Jason Pinkstaff; Zhihua Li; Lillian Skidmore; Nina Li; Heather Myler; Qing Dallas-Yang; Anna-Maria A. Hays Putnam; Jun Yao; Stuart Bussell; Margaret Wu; Thea Norman; Carlos G. Rodriguez; Bruce E. Kimmel; Joseph M. Metzger; Anthony Manibusan; Darin Lee; Dennis M. Zaller; Bei B. Zhang; Richard D. DiMarchi; Joel P. Berger; Douglas W. Axelrod
Fibroblast growth factor 21 (FGF21) mitigates many of the pathogenic features of type 2 diabetes, despite a short circulating half-life. PEGylation is a proven approach to prolonging the duration of action while enhancing biophysical solubility and stability. However, in the absence of a specific protein PEGylation site, chemical conjugation is inherently heterogeneous and commonly leads to dramatic loss in bioactivity. This work illustrates a novel means of specific PEGylation, producing FGF21 analogs with high specific activity and salutary biological activities. Using homology modeling and structure-based design, specific sites were chosen in human FGF21 for site-specific PEGylation to ensure that receptor binding regions were preserved. The in vitro activity of the PEGylated FGF21 ana-logs corresponded with the site of PEG placement within the binding model. Site-specific PEGylated analogs demonstrated dramatically increased circulating half-life and enhanced efficacy in db/db mice. Twice-weekly dosing of an optimal FGF21 analog reduced blood glucose, plasma lipids, liver triglycerides, and plasma glucagon and enhanced pancreatic insulin content, islet number, and glucose-dependent insulin secretion. Restoration of insulin sensitivity was demonstrated by the enhanced ability of insulin to induce Akt/protein kinase B phosphorylation in liver, muscle, and adipose tissues. PEGylation of human FGF21 at a specific and preferred site confers superior metabolic pharmacology.
Archive | 2008
Thomas P. Cujec; Roberto Mariani; Anna-Maria A. Hays Putnam; William M. Keefe; Nick Knudsen; Lillian Ho; Jason Pinkstaff
Archive | 2007
Joseph Sheffer; Thea Norman; Richard D. DiMarchi; Anna-Maria A. Hays Putnam; Feng Tian; Stephanie Chu; Denise Krawitz; Ho Sung Cho
Archive | 2009
Jason Pinkstaff; Anna-Maria A. Hays Putnam; Kristin S Eaton
Archive | 2008
Zhenwei Miao; Denise Krawitz; Feng Tian; Bee-Cheng Sim; Lillian Skidmore; Anna-Maria A. Hays Putnam; Nick Knudsen; Michael Deguzman
Archive | 2006
Zhenwei Miao; Feng Tian; Anna-Maria A. Hays Putnam; Ying Buechler
Archive | 2009
Anna-Maria A. Hays Putnam; Nick Knudsen; Jason Pinkstaff; Heather Myler; Lorraine Sullivan
Archive | 2009
Anna-Maria A. Hays Putnam; Nick Knudsen; Thea Norman; Alan Koder; Lillian Ho; Peter C. Canning
Archive | 2008
Nick Knudsen; Anna-Maria A. Hays Putnam; Denise Krawitz; Jason Pinkstaff; Heather Myler